Статті в журналах з теми "Morris wate maze behaviour paradigm"

Abstract Pycnanthus angolensis (Welw) Warb., Myristicaceae, is used extensively in ethnomedicine. Numerous health benefits have been ascribed to the use of different parts of P. angolensis including its role in cognitive function and inflammatory conditions. Hence, this study was undertaken to investigate the effect of stem bark of the plant on memory function in mice.The plant material was pulverized into powder and extracted by maceration with 80% methanol at room temperature for 48 h. This was subsequently fractionated using N-hexane, Dichloromethane (DCM) and Ethyl acetate. The Dichloromethane fraction which is the most potent fraction (25, 50 and 100 mg/kg) was evaluated for memory enhancing activity using the Y-maze (YMT), morris water maze (MWM) and the elevated plus maze (EPM) on D-galactose plus scopolamine and ketamine induced amnesia. The antioxidant markers and acetylcholinesterase (AChE) inhibiting effect of DCM were also investigated.The results obtained from the behavioural study indicates that the DCM fraction significantly (p<0.05) increased alternation behaviour of mice in the YMT, decreased the escape latency in the MWM paradigm and decreased the transfer latency in the EPM. Biochemically, DCM increased glutathione, and superoxide dismutase, but decreased malondialdehyde and AChE activity in the brain.The findings therefore suggests that the DCM possesses significant memory enhancing activity, which may be due to enhancement of antioxidant activity and cholinergic transmission. The attenuation of the effect of ketamine by the DCM may possibly result from an increase in NMDA receptor mediated neurotransmission and attenuation of oxidative stress.

Spatial navigation is a universal behavior that varies depending on goals, experience and available sensory stimuli. Spatial navigational tasks are routinely used to study learning, memory and goal-directed behavior, in both animals and humans. One popular paradigm for testing spatial memory is the Morris water maze, where subjects learn the location of a hidden platform that offers escape from a pool of water. Researchers typically express learning as a function of the latency to escape, though this reveals little about the underlying navigational strategies. Recently, a number of studies have begun to classify water maze search strategies in order to clarify the precise spatial and mnemonic functions of different brain regions, and to identify which aspects of spatial memory are disrupted in disease models. However, despite their usefulness, strategy analyses have not been widely adopted due to the lack of software to automate analyses. To address this need we developed Pathfinder, an open source application for analyzing spatial navigation behaviors. In a representative dataset, we show that Pathfinder effectively characterizes the development of highly-specific spatial search strategies as male and female mice learn a standard spatial water maze. Pathfinder can read data files from commercially- and freely-available software packages, is optimized for classifying search strategies in water maze paradigms, and can also be used to analyze 2D navigation by other species, and in other tasks, as long as timestamped xy coordinates are available. Pathfinder is simple to use, can automatically determine pool and platform geometry, generates heat maps, analyzes navigation with respect to multiple goal locations, and can be updated to accommodate future developments in spatial behavioral analyses. Given these features, Pathfinder may be a useful tool for studying how navigational strategies are regulated by the environment, depend on specific neural circuits, and are altered by pathology.

Spatial navigation is a universal behavior that varies depending on goals, experience and available sensory stimuli. Spatial navigational tasks are routinely used to study learning, memory and goal-directed behavior, in both animals and humans. One popular paradigm for testing spatial memory is the Morris water maze, where subjects learn the location of a hidden platform that offers escape from a pool of water. Researchers typically express learning as a function of the latency to escape, though this reveals little about the underlying navigational strategies. Recently, a number of studies have begun to classify water maze search strategies in order to clarify the precise spatial and mnemonic functions of different brain regions, and to identify which aspects of spatial memory are disrupted in disease models. However, despite their usefulness, strategy analyses have not been widely adopted due to the lack of software to automate analyses. To address this need we developed Pathfinder, an open source application for analyzing spatial navigation behaviors. In a representative dataset, we show that Pathfinder effectively characterizes the development of highly-specific spatial search strategies as male and female mice learn a standard spatial water maze. Pathfinder can read data files from commercially- and freely-available software packages, is optimized for classifying search strategies in water maze paradigms, and can also be used to analyze 2D navigation by other species, and in other tasks, as long as timestamped xy coordinates are available. Pathfinder is simple to use, can automatically determine pool and platform geometry, generates heat maps, analyzes navigation with respect to multiple goal locations, and can be updated to accommodate future developments in spatial behavioral analyses. Given these features, Pathfinder may be a useful tool for studying how navigational strategies are regulated by the environment, depend on specific neural circuits, and are altered by pathology.

The morris water maze (MWM) was developed by morris as a device to investigate spatial learning and memory in laboratory rats. MWM has become one of the most frequently used laboratory tools in behavioral neuroscience. The MWM task has been often used in the validation of rodent models for neurocognitive disorders (e.g., Parkinson, Alzheimer, Epilepsy, and Schizophrenia), and the evaluation of possible neurocognitive treatments. It is also being used to assess the properties of established potential antipsychotics in animal models of Schizophrenia. The MWM task requires rats to find a hidden platform in a large, circular pool of water that is colored opaque with powdered non-fat milk (or) non-toxic tempera paint where they must swim to the hidden platform. Because they are in the opaque water, the animals cannot see the platform and cannot rely on scent to find the escape route. Instead, they must rely on extra-maze cues. The behavior of rat can be evaluated by analyzing the different parameters such as escape latency, swim speed, and path length, and probe trail. The purpose of this review is to briefly describe procedural aspects, interpretational difficulties of data and advantages of MWM. This paradigm has become a benchmark test for learning and memory difficulties in animal models and preclinical research in general.

<abstract> <p>The stress response is attached to psychosomatic and psychiatric disorders. Therefore, it is important to comprehend the underlying mechanisms influencing this relationship. Moreover, men and women respond differently to stress–both psychologically and biologically. These differences should be studied to have an enhanced understanding of the gender difference. However, researches shedding light on sex dimorphism implication have historically been insufficient. Based on observations that advocate the inclusion of sex as a biological variable in stress response, the present study was designed to explore sex differences in (i) depressive-like, (ii) anxiety-like behaviors, (iii) cognitive-like performances, and (iv) voluntary ethanol intake (VEI) in Wistar rat submitted to dexamethasone (DEX)-stress simulation. Rats were administered daily with DEX (1.5 mg/kg, s.c., 21 days) or vehicle. Behavior, cognitive, and VEI states of rats were evaluated in the following paradigms: forced swimming test (FST); saccharin preference test (SPT); open field test (OFT); elevated plus-maze test (EPMT); novelty suppressed feeding test (NSFT); spatial learning and memory in Morris water maze test (MWMT); VEI in two-bottle choice paradigm. DEX-treated rats showed a set of depression-like behaviors: increased time of immobility; reduced preference for saccharin consumption; increased anxiety-like behavior; cognitive impairments; and enhanced VEI. Sexual dimorphism was recorded in this study. Females were more impaired in FST, SPT, EPMT, NSFT, and VEI. Results demonstrate that DEX-treatment induced a behavioral alterations related to anxiety-depressive-like state with learning and memory impairments; confirm the facilitatory role of glucocorticoids on VEI and reveal sexual dimorphism in stress response.</p> </abstract>

The execution of agricultural activities on an industrial scale has led to indiscriminate deposition of toxic xenobiotics, including organophosphates, in the biome. This has led to intoxication characterized by deleterious oxidative and neuronal changes. This study investigated the consequences of oxidative and neurogenic disruptions that follow exposure to a combination of two organophosphates, chlorpyrifos (CPF) and dichlorvos (DDVP), on neuro-cognitive performance and anxiety-like behaviors in rats. Thirty-two adult male Wistar rats (150–170 g) were randomly divided into four groups, orally exposed to normal saline (NS), DDVP (8.8 mg/kg), CPF (14.9 mg/kg), and DDVP + CPF for 14 consecutive days. On day 10 of exposure, anxiety-like behavior and amygdala-dependent fear learning were assessed using open field and elevated plus maze paradigms, respectively, while spatial working memory was assessed on day 14 in the Morris water maze paradigm, following three training trials on days 11, 12, and 13. On day 15, the rats were euthanized, and their brains excised, with the hippocampus and amygdala removed. Five of these samples were homogenized and centrifuged to analyze nitric oxide (NO) metabolites, total reactive oxygen species (ROS), and acetylcholinesterase (AChE) activity, and the other three were processed for histology (cresyl violet stain) and proliferative markers (Ki67 immunohistochemistry). Marked (p ≤0.05) loss in body weight, AChE depletion, and overproduction of both NO and ROS were observed after repeated exposure to individual and combined doses of CPF and DDVP. Insults from DDVP exposure appeared more severe owing to the observed greater losses in the body weights of exposed rats. There was also a significant (p ≤0.05) effect on the cognitive behaviors recorded from the exposed rats, and these deficits were related to the oxidative damage and neurogenic cell loss in the hippocampus and the amygdala of the exposed rats. Taken together, these results provided an insight that oxidative and neurogenic damage are central to the severity of neuro-cognitive dysfunction and increased anxiety-like behaviors that follow organophosphate poisoning.

A new hypothesis highlights sleep-dependent learning/memory consolidation and regards the sleep-wake cycle as a modulator of β-amyloid and tau Alzheimer’s disease (AD) pathologies. Sundowning behavior is a common neuropsychiatric symptom (NPS) associated with dementia. Sleep fragmentation resulting from disturbances in sleep and circadian rhythms in AD may have important consequences on memory processes and exacerbate the other AD-NPS. The present work studied the effect of training time schedules on 12-month-old male 3xTg-AD mice modeling advanced disease stages. Their performance in two paradigms of the Morris water maze for spatial-reference and visual-perceptual learning and memory were found impaired at midday, after 4 h of non-active phase. In contrast, early-morning trained littermates, slowing down from their active phase, exhibited better performance and used goal-directed strategies and non-search navigation described for normal aging. The novel multitarget anticholinesterasic compound AVCRI104P3 (0.6 µmol·kg−1, 21 days i.p.) exerted stronger cognitive benefits than its in vitro equipotent dose of AChEI huprine X (0.12 μmol·kg−1, 21 days i.p.). Both compounds showed streamlined drug effectiveness, independently of the schedule. Their effects on anxiety-like behaviors were moderate. The results open a question of how time schedules modulate the capacity to respond to task demands and to assess/elucidate new drug effectiveness.

Aim: Endogenous agmatine has a significant role in learning and memory processes as a neurotransmitter. Various studies described the physiological role of endogenous agmatine in learning and memory of multiple cognitive tasks suggesting elevated levels of agmatine during the learning process in the rat brain. Dietary intake of choline showed correlation with cognitive functions in human subjects and treatment with choline supplements validated the ability to diminish learning and cognitive impairment dementias. Methods: 36 Albino rats were equally divided into three groups previously: a) control-water, b) Test I - AlCl3 (100 mg/Kg body weight), and c) Test II - Forced swim stress (FSS) for 14 days. On the next day of AlCl3 and FSS last administration, animals were allocated into further three groups and received the following treatments: a. water was given orally to the control group, b. Agmatine (100 mg/Kg Body Weight) group, and c. Choline (100 mg/Kg Body Weight) group for the next 14 days. Behaviors were assessed in Light/Dark Box, Open Field, Novel Object Recognition Test (NOR), T Maze Test, and Morris Water Maze Test. Results: Animals administered with agmatine demonstrated increased time spent in bright areas of light/dark box and square crossed while improved spatial memory in Morris water maze and T maze test and enhanced discrimination of novel object in NOR were observed in learning and memory paradigms along with choline. Conclusion: The present study determines that agmatine at the dose of (100 mg/kg body weight) attenuates memory and cognitive impairment in comparison with choline supplements.

The search for potential effective antidepressants with minimal side effects is necessary. Peptides are possible applicants for this role. We investigated the antidepressant effect of neuropeptide Y (NY), alone and in combination with clomipramine, in models of acute and chronic stress induced by ultrasound of variable frequencies. Rats were divided into the following groups: the control group, stress group, and stress groups with intranasal administration of NY (100 μg/kg) or clomipramine (7.5 mg/kg), or their combination. Rat behavior was evaluated using a sucrose preference test and forced swimming test in an acute stress model, and a sucrose preference test, forced swimming test, social interaction test, open field test, and Morris water maze test in a chronic stress model. The results of our experiment demonstrated a protective effect of intranasal NY in a model of acute stress, which was comparable to the antidepressant effect of clomipramine. When the same dose was chronically administered, NY also demonstrated an antidepressant action, although expressed in a lesser degree than clomipramine. The combination of NY and clomipramine was much less effective in the chronic stress paradigm compared to the separated drug administration, but was just as effective in the acute stress paradigm. Until now, there was no convincing evidence for the efficacy of the chronic administration of neuropeptide Y; we demonstrated its effectiveness in the animal model of depressive-like behavior. However, our hypothesis that neuropeptide Y can enhance the effect of a classical antidepressant was not confirmed.

Free-living animals rely on cognitive functions, such as learning and memory, for numerous aspects of their survival. However, research involving these mechanisms is often limited to the laboratory where animals are far removed from natural influences. Here, we adapted the Morris Water Maze (MWM) for use in the field to test learning and memory of free-living white-footed mice, Peromyscus leucopus. The MWM consists of a pool filled with opaque water and a platform that is hidden beneath the surface of the water. Mice were tasked with finding an escape platform using proximate-cue based spatial learning skills across trials within and between two tests. The two tests occurred 2 hrs apart and each consisted of 5 trials with a maximum search time of 60 s, separated by 15-s breaks. We found mice demonstrated rapid learning within the first 5 trials, as indicated by a faster time and reduced distanced swam to find the platform in trial 5 as compared to trial 1 in Test 1. We also found mice remembered the task, as indicated by equivalent performance (in time and distance) after the two-hour delay period (i.e., performance in Test 2 trial 1 was similar to that in Test 1 trial 5). Lastly, we found that there was no increase in performance as mice completed an additional 5 trials (i.e., no difference in Test 1 trial 5 vs. Test 2 trial 5). By assessing several variables that serve as standard metrics for learning and memory within the MWM, we were able to illustrate the ability of wild mice to successfully navigate within a modified version of an established learning/memory paradigm. This study is important for promoting more accessible forms of cognitive testing in free-living animals and use of such a method could provide insights into how animals cope with environmental stressors in their natural environment such as anthropogenic disturbance, invasive species, and habitat degradation. A better understanding of cognitive behavior in wild animals may help diminish the disparity of knowledge that is often present between laboratory and field research.

To assess the long-term behavioral effects of repetitive mild traumatic brain injury (rmTBI), we employed a preclinical model of rmTBI and performed a battery of behavioral tests starting 14 weeks post-injury. Male Sprague-Dawley rats received four unilateral mild (6 m/s; 0.5 mm depth) controlled cortical impacts (CCI), centered 4 mm posterior and 3–4 mm lateral to the bregma, administered at five-day intervals. The animals’ weights were monitored throughout the study. We tested the rats for anxiety-like (elevated plus maze, open field test), depression-like (forced swim test), locomotor (rotarod, open field test), and spatial learning and memory (Morris water maze (MWM)) behavioral deficits. Overall, a mild behavioral phenotype was observed. Significant deficits were observed with the MWM, indicating that our injury model disrupts spatial learning and memory. An interesting aspect of these data is a directional/visual component to the spatial learning and memory deficits dependent on the zone in which the trial began. With the injury being unilateral, there may be an imbalance in visual acuity that contributes to the observed deficits. Analysis of weight gain data demonstrated that rmTBI reduces weight during the period while injuries are occurring. This may represent another measure that can be tracked to determine injury severity and recovery. RNA-seq analysis demonstrated that gene expression at the chronic endpoint could distinguish between the experimental groups even with a mild behavioral phenotype. Future studies would include a more severe injury paradigm to promote longer-lasting behavior changes.

Objective: The purpose of this study was to examine the effect of exposure of a low-intensity blast wave on androgen receptor (AR) density in the hippocampus and the potential influence on behavioral and cognitive responses. Methods: Sprague-Dawley rats were randomly assigned to either a blast exposed group (n = 27) or an unexposed (control) group (n = 10). Animals were treated identically, except that rats within the control group were not exposed to any of the characteristics of the blast wave. Behavior measures were conducted on day seven post-exposure. The rats were initially assessed in the elevated plus maze followed by the acoustic startle response paradigm. Spatial memory performance using the Morris water-maze test was assessed at 8-days post-exposure, for seven consecutive days. Following all behavioral tests AR immunofluorescence staining was performed in different hippocampal subregions. Results: A significant elevation in anxiety index (p < 0.001) and impaired learning (p < 0.015) and spatial memory (p < 0.0015) were noted in exposed rats. In addition, a significant attenuation of the AR was noted in the CA1 (p = 0.006) and dentate gyrus (p = 0.031) subregions of the hippocampus in blast exposed animals. Correlational analyses revealed significant associations between AR and both anxiety index (r = –.36, p = 0.031) and memory (r = –0.38, p = 0.019). Conclusions: The results of this study demonstrate that exposure to a low-pressure blast wave resulted in a decrease in AR density, which was associated with significant behavioral and cognitive changes.

Increasing evidence suggests that cyclin-dependent kinases participate in neuronal death induced by multiple stresses in vitro. However, their role in cell death paradigms in vivo is not well characterized. Accordingly, the authors examined whether cyclin-dependent kinase inhibition resulted in functionally relevant and sustained neuroprotection in a model of global ischemia. Intracerebroventricular administration of the cyclin-dependent kinase inhibitor flavopiridol, immediately or at 4 hours postreperfusion after a global insult, reduced injury in the CA1 of the hippocampus when examined 7 days after reperfusion. No significant protection was observed when flavopiridol was administered 8 hours after reperfusion. The tumor-suppressor retinoblastoma protein, a substrate of cyclin-dependent kinase, was phosphorylated on a cyclin-dependent kinase consensus site after the global insult; this phosphorylation was inhibited by flavopiridol administration. Importantly, flavopiridol had no effect on core body temperature, suggesting that the mechanism of neuroprotection was through cyclin-dependent kinase inhibition but not through hypothermia. Furthermore, inhibition of cyclin-dependent kinases improved spatial learning behavior as assessed by the Morris water maze 7 to 9 days after reperfusion. However, the histologic protection observed at day 7 was absent 28 days after reperfusion. These results indicate that cyclin-dependent kinase inhibition provides an extended period of morphologic and functional neuroprotection that may allow time for other neuroprotective modalities to be introduced.

Postnatal growth failure is a common morbidity for preterm infants and is associated with adverse neurodevelopmental outcomes. Although sodium (Na) deficiency early in life impairs somatic growth, its impact on neurocognitive functions has not been extensively studied. We hypothesized that Na deficiency during early life is sufficient to cause growth failure and program neurobehavioral impairments in later life. C57BL/6J mice were placed on low- (0.4), normal- (1.5), or high- (3 g/kg) Na chow at weaning ( PD22) and continued on the diet for 3 wk (to PD40). Body composition and fluid distribution were determined serially by time-domain NMR and bioimpedance spectroscopy, and anxiety, learning, and memory were assessed using the elevated plus maze and Morris water maze paradigms in later adulthood ( PD63– PD69). During the diet intervention, body mass gains were suppressed in the low- compared with normal- and high-Na groups despite similar caloric uptake rates across groups. Fat mass was reduced in males but not in females fed low-Na diet. Fat-free mass and hydration were significantly reduced in both males and females fed the low-Na diet, although rapidly corrected after return to normal diet. Measures of anxiety-like behavior and learning in adulthood were not affected by diet in either sex, yet memory performance was modified by a complex interaction between sex and early life Na intake. These data support the concepts that Na deficiency impairs growth and that the amount of Na intake which supports optimal somatic growth during early life may be insufficient to fully support neurocognitive development.

Mental disorders are psychological symptoms that impact multiple areas of an individual’s life. Depression and anxiety are chronic illnesses described as the most prevalent stress-related mood disorders that cause injury and early death. In Morocco, Anise “Pimpinella anisum L.” is one of the most traditionally used condiment plants, which has long been used to cure various illnesses and in phytotherapy. The present study was designed to investigate the antidepressant, anxiolytic, and memory impact of the total extract of Pimpinella anisum (PATE) at the doses of 100 and 200 mg/kg, using the Forced Swimming Test (FST), Tail Suspension Test (TST), Open Field Test (OFT), and Light–Dark Box Test (LDBT) as an experimental paradigm of anxiety and depression, and Novel Object Recognition Test (NORT) and the Morris Water Maze Test (MWMT) as memory tests on Swiss albino mice. The tests were carried out on the 1st, 7th, 14th, and the 21st days of the study, and the extract groups were compared with normal controls and positive controls (receiving bromazepam and paroxetine at the doses of 1 mg/kg and 11.5 mg/kg for anxiety and depression, respectively). The daily oral gavage of the mice by the PATE induced a significant anxiolytic and antidepressant-like effect by shortening immobility time and decreasing downtime in the different tests. PATE at both doses was shown to have no impact on memory following the NORT and MWM tests. Different compounds, such as gallic acid, catechin, chlorogenic acid, caffeic acid, oleuropein, p-coumaric acid, trans-4-hydroxy-3-methoxycinnamic acid, myricetin, and quercetin, were identified during the phytochemical analysis carried out using HPLC analysis. This research supports and promotes the extract’s traditional use, suggesting its use as a phytomedicine against depression and anxiety, and calls for further research to clarify its mode of action.

Mild behavioral deficits, which are part of normal aging, can be early indicators of an impending Alzheimer's disease. Using the APPswe/PS1dE9 (APP/PS1) mouse model of Alzheimer's disease, we utilized the Morris water maze spatial learning paradigm to systematically evaluate mild behavioral deficits that occur during the early stages of disease pathogenesis. Conventional behavioral analysis using this model indicates that spatial memory is intact at 2 months of age. In this study, we used an alternative method to analyze the behavior of mice, aiming to gain a better understanding of the nature of cognitive deficits by focusing on the unsuccessful trials during water maze learning rather than on the successful ones. APP/PS1 mice displayed a higher number of unsuccessful trials during the initial days of training, unlike their wild-type counterparts. However, with repeated trial and error, learning in APP/PS1 reached levels comparable to that of the wild-type mice during the later days of training. Individual APP/PS1 mice preferred a non-cognitive search strategy called circling, which led to abrupt learning transitions and an increased number of unsuccessful trials. These findings indicate the significance of subtle intermediate readouts as early indicators of conditions such as Alzheimer's disease.

Mild behavioral deficits, which are part of normal aging, can be early indicators of an impending Alzheimer's disease. Using the APPswe/PS1dE9 (APP/PS1) mouse model of Alzheimer's disease, we utilized the Morris water maze spatial learning paradigm to systematically evaluate mild behavioral deficits that occur during the early stages of disease pathogenesis. Conventional behavioral analysis using this model indicates that spatial memory is intact at 2 months of age. In this study, we used an alternative method to analyze the behavior of mice, aiming to gain a better understanding of the nature of cognitive deficits by focusing on the unsuccessful trials during water maze learning rather than on the successful ones. APP/PS1 mice displayed a higher number of unsuccessful trials during the initial days of training, unlike their wild-type counterparts. However, with repeated trial and error, learning in APP/PS1 reached levels comparable to that of the wild-type mice during the later days of training. Individual APP/PS1 mice preferred a non-cognitive search strategy called circling, which led to abrupt learning transitions and an increased number of unsuccessful trials. These findings indicate the significance of subtle intermediate readouts as early indicators of conditions such as Alzheimer's disease.

AbstractSulpiride, as a D2-like dopamine (DA) receptor (D2R) antagonist, is an important antipsychotic drug in the treatment of schizophrenia. Recently, we have shown that the activation of D2Rs in the ventral pallidum (VP) modulates the activity of the ventral tegmental area (VTA) DAergic neurons. According to our hypothesis, intra-VP sulpiride can influence the motivational and learning processes, pervasively modifying the behavior of examined animals. In the present study, sulpiride was microinjected into the VP of male Wistar rats in three different doses. Morris water maze (MWM) test was applied to investigate the effects of sulpiride on spatial learning, while conditioned place preference (CPP) test was used to examine the potential rewarding effect of the drug. In order to show, whether the animals can associate the rewarding effect with an area which can be recognized only on its spatial location, we introduced a modified version of the CPP paradigm, the spatial CPP test. Our results show that the intra-VP sulpiride dose-dependently impairs learning processes. However, the largest dose of sulpiride induces place preference. Results of the spatial CPP paradigm demonstrate that the animals cannot associate the rewarding effect of the drug with the conditioning area based on its spatial location. In the CPP paradigm, locomotor activity decrease could be observed in the sulpiride-treated rats, likely because of a faster habituation with the conditioning environment. In summary, we can conclude that intra-VP sulpiride has a dual effect: it diminishes the hippocampus-dependent spatial learning processes, in addition, it has a dose-dependent rewarding effect.

Recent investigations have demonstrated that the chronic stress-induced behavioral disorders can be ameliorated by probiotics including Clostridium butyricum (C. butyricum) via the gut-brain-axis. However, the molecular mechanisms underlying the beneficial effects of C. butyricum on brain remain largely unknown. Here, we investigated whether chronic foot shock stress (CFSS) paradigm used for a hypertensive animal model could induce mood disorders such as anxiety, depression and cognitive impairments. Then, we assessed the impact of C. butyricum RH2 on the behavior disorders and neurobiological alterations in the hippocampus. Male Sprague-Dawley (SD) rats received intermittent electric shocks for consecutive 14 days and were treated with C. butyricum RH2 for 17 days. Anxiety- or depression-like behaviors were evaluated by open field test (OFT), and elevated plus maze (EPM). The Morris water maze test (MWM) was used to evaluate the cognitive functions. CFSS intervention led to mild anxiety- or depression-like behavior or cognitive impairment and C. butyricum RH2 treatment reversed the CFSS-induced symptoms. The serum ACTH or CORT was increased following CFSS but was completely reversed by C. butyricum RH2 treatment. In the hippocampus of CFSS rats, the expressions of BDNF and TrkB were downregulated but proBDNF and P75NTR were upregulated. These expression changes were partially reversed by C. butyricum RH2, suggesting a mode of action on BDNF and proBDNF balance. CFSS exposure resulted in downregulation of tissue-type plasminogen activator (tPA) but upregulation of plasminogen activator inhibitor 1(PAI-1), which could contribute to the decrease in BDNF by reduced conversion from proBDNF to BDNF in the hippocampus. C. butyricum RH2 treatment reversed the upregulated PAI-1 but not the downregulated tPA, which was in parallel with the amelioration of behavioral abnormalities, suggesting a novel tPA independent mechanism for PAI-1 action. Our results demonstrate for the first time that C. butyricum RH2 attenuates stress-induced behavior disorders via inhibiting the expression of brain PAI-1.

Binge-like ethanol exposure during adolescence has been shown to produce long lasting effects in animal models including anxiety-like behavior that can last into young adulthood and impairments in cognition that can last throughout most of the lifespan. However, little research has investigated if binge-like ethanol exposure during adolescence produces persistent anxiety-like behavior and concomitantly impairs cognition late in life. Furthermore, few studies have investigated such behavioral effects in both female and male rats over the lifespan. Finally, it is yet to be determined if binge-like ethanol exposure during adolescence alters microglia activation in relevant brain regions late in life. In the present study female and male adolescent rats were exposed to either 3.0 or 5.0 g/kg ethanol, or water control, in a chronic intermittent pattern before being tested in the elevated plus maze and open field task over the next ∼18 months. Animals were then trained in a spatial reference task via the Morris water maze before having their behavioral flexibility tested. Finally, brains were removed, sectioned and presumptive microglia activation determined using autoradiography for [3H]PK11195 binding. Males, but not females, displayed an anxiety-like phenotype initially following the chronic intermittent ethanol exposure paradigm which resolved in adulthood. Further, males but not females had altered spatial reference learning and impaired behavioral flexibility late in life. Conversely, [3H]PK11195 binding was significantly elevated in females compared to males late in life and the level of microglia activation interacted as a function of sex and brain regions, but there was no long-term outcome related to adolescent alcohol exposure. These data further confirm that binge-like ethanol exposure during adolescence produces alterations in behavior that can last throughout the lifespan. In addition, the data suggest that microglia activation late in life is not exacerbated by prior binge-like ethanol exposure during adolescence but the expression is sex- and brain region-dependent across the lifespan.

Background: Increased exposure of humans to toxic metals and high fat diet (HFD) consumption severely damages brain health. Natural plant extracts have shown huge potential to treat multiple human diseases. Objective: The present study was designed to evaluate the protective effects of Shogaol (an active component of ginger) in neuroinflammation and behavioral paradigms in mice treated with metals and HFD. Methods: 8-11 weeks old male mice model was developed by giving a combination of metals i.e. Arsenic (As), Lead (Pb) and Aluminum (Al), 25mg/kg each mixed in drinking water with laboratory prepared HFD (40% fat) for a total duration of 72 days. Shogaol treated groups received two doses (2mg/kg & 12mg/kg) of shogaol along with metals and HFD. The biochemical parameters including body weights, blood glucose, kidney and liver functions were assessed along with the integrity of blood brain barrier (BBB). The expression analysis of neuroinflammatory genes (TNF-α, IL-1β & GFAP) was performed using q-PCR in the hippocampus and cortex. The exploratory and anxiety like behavior was assessed using open filed, and depressive behavior was assessed through forced swim test, while learning and memory were assessed using Morris water maze test and y- maze test. Results: Shogaol (2mg/kg & 12mg/kg) treatment improved metabolic profile and reduced expression of neuroinflammatory genes in the cortex and the hippocampus. Shogaol treatment improved BBB integrity. Results of behavioral analysis showed that Shogaol treatment (2mg/kg & 12mg/kg) rescued behavioral impairment and improved anxiety and depression. Conclusion: Shogaol treatment showed strong therapeutic potential in metals & HFD induced neuroinflammation and improved cognitive functions, thus, can be considered as a potential drug candidate in future.

The purpose of this study was to determine preventive and protective effects of chronic orally administration with quetiapine (QUE) against anxiety-like behavior and cognitive impairments in rats exposed to the enhanced single prolonged stress (ESPS), an animal model that is used to study post-traumatic stress disorder (PTSD), and to detect changes in the expression of cortical phosphorylated p44/42 extracellular-regulated protein kinase (pERK1/2). Before or after exposure to ESPS paradigm, consisting of 2-h constraint, 20-min forced swimming, etherinduced loss of consciousness, and an electric foot shock, rats were given orally QUE (10 mg/kg daily) for 14 days. Animals were then tested in the open field (OF), elevated plus-maze (EPM), and Morris water maze (MWM). Brains were removed for immunohistochemical staining of pERK1/2. ESPS exposure resulted in pronounced anxiety-like behavior compared to unexposed animals. ESPS-exposed animals also displayed marked learning and spatial memory impairments. However, QUE treatment (both before and after ESPS exposure) significantly ameliorated anxiety-like behavior, learning and spatial memory impairments. ESPS also markedly reduced the expression of pERK1/2 in the prefrontal cortex, medial amygdala nucleus, and cingulate gyrus. Both before and after ESPS exposure QUE treatments significantly elevated the reduced pERK1/2 expression in the three brain regions. QUE has preventive and protective effects against stress-associated symptoms and the changes in pERK1/2 functions may be associated with the pathophysiology of traumatic stress and the therapeutic efficacy of anti-PTSD therapy.

Reinforcement learning (RL) has become a popular paradigm for modeling animal behavior, analyzing neuronal representations, and studying their emergence during learning. This development has been fueled by advances in understanding the role of RL in both the brain and artificial intelligence. However, while in machine learning a set of tools and standardized benchmarks facilitate the development of new methods and their comparison to existing ones, in neuroscience, the software infrastructure is much more fragmented. Even if sharing theoretical principles, computational studies rarely share software frameworks, thereby impeding the integration or comparison of different results. Machine learning tools are also difficult to port to computational neuroscience since the experimental requirements are usually not well aligned. To address these challenges we introduce CoBeL-RL, a closed-loop simulator of complex behavior and learning based on RL and deep neural networks. It provides a neuroscience-oriented framework for efficiently setting up and running simulations. CoBeL-RL offers a set of virtual environments, e.g., T-maze and Morris water maze, which can be simulated at different levels of abstraction, e.g., a simple gridworld or a 3D environment with complex visual stimuli, and set up using intuitive GUI tools. A range of RL algorithms, e.g., Dyna-Q and deep Q-network algorithms, is provided and can be easily extended. CoBeL-RL provides tools for monitoring and analyzing behavior and unit activity, and allows for fine-grained control of the simulation via interfaces to relevant points in its closed-loop. In summary, CoBeL-RL fills an important gap in the software toolbox of computational neuroscience.

Huntington's disease (HD), a neurodegenerative condition specified by mitochondrial deficits, psychiatric and cognitive impairment developed due to neuronal damage in the brain. 3-nitropropionic acid (3-NP), an inhibitor of succinate dehydrogenase develops behavioral, biochemical as well as histological alterations in the striatal region of brain, which resembles HD in humans. Phosphodiesterases (PDEs) participate in cognition, motor functions, and behavior as well as also offers neuroprotection. The present investigation was framed to analyze the neuro-defensive characteristics of cilostazol PDE3 inhibitor over the 3-NP induced behavioral, striatal and mitochondrial deficits. Administration of 3-NP (10mg kg-1; i.p.) for the duration of 14 days has shown considerable alterations in behavior such as decreased locomotion (actophotometer), reduced grip strength (rota-rod test), spatial learning memory (elevated plus maze and Morris water maze). In parallel to, 3-NP treated rats exhibit biochemical changes such as increased oxidative stress (enhanced lipid peroxides, reduced glutathione, catalase, and superoxide dismutase), disturbed cholinergic function (increased acetylcholinesterase activity), increased inflammation (more myeloperoxidase) and mitochondrial dysfunction (reduced complex I, II and IV activity). Histopathological changes (Nissl stain) like chronic neuronal gap, pyknotic nuclei as well as injured cells in the cerebral cortex and hippocampus were also observed in 3-NP treated rats. Administration of cilostazol considerably restored behavioral abnormalities, biochemical and histopathological alterations. In this investigation, cilostazol offered neurodefensive effects which were established by behavioral and biochemical paradigms, which confirmed the potent neurodefensive aspect of cilostazol in 3-NP provoked behavioral and biochemical abnormalities.

BackgroundInadequate sleep during pregnancy negatively affects the neural development of offspring. Previous studies have focused on the continuous sleep deprivation (CSD) paradigm, but the sleep pattern during late pregnancy is usually fragmented.ObjectiveTo compare the effects of CSD and fragmented sleep deprivation (FSD) in late pregnancy on emotion, cognition, and expression of synaptic plasticity-related proteins in offspring mice.MethodsPregnant CD-1 mice were either subjected to 3/6 h of CSD/FSD during gestation days 15–21, while those in the control group were left untreated. After delivery, the offspring were divided into five groups, i.e., control (CON), short or long CSD (CSD3h, CSD6h), and short or long FSD (FSD3h, FSD6h). When the offspring were 2 months old, the anxiety-like behavior level was tested using the open field (OF) and elevated plus maze (EPM) test, and spatial learning and memory were evaluated using the Morris water maze (MWM) test. The expression of hippocampal of brain-derived neurotrophic factor (Bdnf) and synaptotagmin-1 (Syt-1) was determined using RT-PCR and western blotting.ResultsThe CSD6h, FSD3h, and FSD6h had longer latency, fewer center times in the OF test, less open arms time and fewer numbers of entries in the open arms of the EPM, longer learning distance swam and lower memory percentage of distance swam in the target quadrant in the MWM test, and decreased BDNF and increased Syt-1 mRNA and protein levels in the hippocampus. Compared to the CSD6h, the FSD3h and FSD6h had longer distance swam, a lower percentage of distance swam in the target quadrant, decreased BDNF, and increased Syt-1 mRNA and protein levels in the hippocampus.ConclusionThe results suggested that maternal sleep deprivation during late pregnancy impairs emotion and cognition in offspring, and FSD worsened the cognitive performance to a higher extent than CSD. The observed cognitive impairment could be associated with the expression of altered hippocampal of Bdnf and Syt-1 genes.

Exposure to elevated doses of ionizing radiation, such as those in therapeutic procedures, catastrophic accidents, or space exploration, increases the risk of cognitive dysfunction. The full range of radiation-induced cognitive deficits is unknown, partly because commonly used tests may be insufficiently sensitive or may not be adequately tuned for assessing the fine behavioral features affected by radiation. Here, we asked whether gamma-radiation might affect learning, memory, and the overall ability to adapt behavior to cope with a challenging environment (cognitive/behavioral flexibility). We developed a new behavioral assay, the context discrimination Morris water maze (cdMWM) task, which is hippocampus-dependent and requires the integration of various contextual cues and the adjustment of search strategies. We exposed male mice to 1 or 5 Gy of gamma-rays and, at different time points after irradiation, assessed learning and memory, and analyzed navigational search strategies in mice trained consecutively in spatial MWM, reversal MWM, and cdMWM tasks. Mice exposed to 5 Gy, performed successfully in the spatial and reversal MWM tasks; however, in the cdMWM task 6 or 8 weeks (but not 3 weeks) after irradiation, they demonstrated transient learning deficit, decreased use of efficient spatially precise search strategies during learning, and memory deficit 6 weeks post-irradiation. We also observed impaired neurogenesis after irradiation and selective activation of 12-week-old newborn neurons by specific components of cdMWM training. Thus, our new behavioral paradigm indicates an extended timeframe for the functional maturation of new hippocampal neurons and reveals the effects of gamma-radiation on cognitive flexibility.Significance Statement:Exposure to radiation can affect cognitive performance and cognitive flexibility – the ability to adapt to changed circumstances and demands. The full range of consequences of irradiation on cognitive flexibility is unknown, partly because of a lack of suitable models. Here, we developed a new behavioral task requiring mice to combine various types of cues and strategies to find a correct solution. We show that animals exposed to gamma-radiation, despite being able to successfully solve standard problems, show delayed learning, deficient memory, and diminished use of efficient navigation patterns in circumstances requiring adjustments of previously used search strategies. This new task could be applied in other settings for assessing the cognitive changes induced by aging, trauma, or disease.

ObjectivesTo explore the relationship between leucine in cerebrospinal fluid (CSF) and cognitive dysfunction in rats with early life stress (ELS) induced mental illness, and pathophysiological mechanism involved.MethodsThe maternal separation (MS), an animal paradigm used widely as a preclinical model of ELS which is one of the important risk factors for mental disorders. Behavioral experiments including open-field test, sucrose preference, object recognition and Morris water maze tests, Nissl staining, transmission electron microscopy and WES were employed in the present study.ResultsThe behavioral results showed that MS rats were more prone to cognitive impairment and depression-and-anxiety-like behaviors than controls, including spatial self-exploration ability, memory ability, and spatial learning and memory function. Nissl staining analysis indicated that the number of neurons in the CA1 and CA3 regions of the hippocampus significantly decreased and the arrangement of nerve cells was abnormal. The leucine levels were decreased in the CSF of MS rats and highly correlated with the number of hippocampal neurons, and yet leucine supplementation improved the degree of MS-induced cognitive impairment. Furthermore, there were autophagosomes in the hippocampus of the low-leucine diet rats of the control and MS group but not in the high-leucine diet MS group by transmission electron microscopy. The protein expression of Beclin-1 in the hippocampus was significantly increased in the MS normal diet group and MS low-leucine diet group, yet decreased in the MS high-leucine diet group compared with the MS low-leucine diet group. Meanwhile, the Bcl-2/Bax ratio was significantly decreased in the control low-leucine diet group, MS normal diet group and MS low-leucine diet group. Ultimately, in vitro experiments suggested that leucine deficiency could activate neuronal autophagy including enhanced LC3II/LC3I and mRFP-GFP-LC3, which was consistent with the in vivo results, and the cell apoptosis rate and lactate dehydrogenase (LDH) cytotoxicity were also increased with leucine deficiency, while the above effects could be partly reversed by autophagy inhibitor treatment.ConclusionsMS model caused adult male rats to be susceptible to cognitive dysfunction, which may regulate autophagy in hippocampal neurons through leucine metabolism in CSF.

AbstractThe intracerebroventricularly (icv) injected streptozotocin (STZ) induced brain state is a widely used model of sporadic Alzheimer-disease (AD). However, data have been generated in young, naive albino rats. We postulate that the translationally most relevant animal population of an AD model should be that of aged rats with substantial learning history. The objective of the study was thus to probe the model in old rats with knowledge in various cognitive domains. Long-Evans rats of 23 and 10 months age with acquired knowledge in five-choice serial reaction time task (5-CSRTT), a cooperation task, Morris water-maze (MWM) and “pot-jumping” exercise were treated with 3 × 1.5 mg/kg icv. STZ and their performance were followed for 3 months in the above and additional behavioral assays. Both STZ-treated age groups showed significant impairment in the MWM (spatial learning) and novel object recognition test (recognition memory) but not in passive avoidance and fear conditioning paradigms (fear memory). In young STZ treated rats, significant differences were also found in the 5CSRTT (attention) and pot jumping test (procedural learning) while in old rats a significant increase in hippocampal phospho-tau/tau protein ratio was observed. No significant difference was found in the cooperation (social cognition) and pairwise discrimination (visual memory) assays and hippocampal β-amyloid levels. STZ treated old animals showed impulsivity-like behavior in several tests. Our results partly coincide with partly deviate from those published on young, albino, unexperienced rats. Beside the age, strain and experience level of the animals differences can also be attributed to the increased dose of STZ, and the applied food restriction regime. The observed cognitive and non-cognitive activity pattern of icv. STZ in aged experienced rats call for more extensive studies with the STZ model to further strengthen and specify its translational validity.

In Australia the “intimacy” of citizenship (Berlant 2), is often used to reinforce subscription to heteronormative romantic and familial structures. Because this framing promotes discourses of moral failure, recent political attention to sexuality and same-sex couples can be filtered through insights into coalitional affiliations. This paper uses contemporary shifts in Australian politics and culture to think through the concept of coalition, and in particular to analyse connections between sexuality and governmentality (or more specifically normative bias and same-sex relationships) in what I’m calling post-coalitional Australia. Against the unpredictability of changing parties and governments, allegiances and alliances, this paper suggests the continuing adherence to a heteronormatively arranged public sphere. After the current Australian Prime Minister Julia Gillard deposed the previous leader, Kevin Rudd, she clung to power with the help of independents and the Greens, and clichés of a “rainbow coalition” and a “new paradigm” were invoked to describe the confused electorate and governmental configuration. Yet in 2007, a less confused Australia decisively threw out the Howard–led Liberal and National Party coalition government after eleven years, in favour of Rudd’s own rainbow coalition: a seemingly invigorated party focussed on gender equity, Indigenous Australians, multi-cultural visibility, workplace relations, Austral-Asian relations, humane refugee processing, the environment, and the rights and obligations of same-sex couples. A post-coalitional Australia invokes something akin to “aftermath culture” (Lambert and Simpson), referring not just to Rudd’s fall or Howard’s election loss, but to the broader shifting contexts within which most Australian citizens live, and within which they make sense of the terms “Australia” and “Australian”. Contemporary Australia is marked everywhere by cracks in coalitions and shifts in allegiances and belief systems – the Coalition of the Willing falling apart, the coalition government crushed by defeat, deposed leaders, and unlikely political shifts and (re)alignments in the face of a hung parliament and renewed pushes toward moral and cultural change. These breakdowns in allegiances are followed by swift symbolically charged manoeuvres. Gillard moved quickly to repair relations with mining companies damaged by Rudd’s plans for a mining tax and to water down frustration with the lack of a sustainable Emissions Trading Scheme. And one of the first things Kevin Rudd did as Prime Minister was to change the fittings and furnishings in the Prime Ministerial office, of which Wright observed that “Mr Howard is gone and Prime Minister Kevin Rudd has moved in, the Parliament House bureaucracy has ensured all signs of the old-style gentlemen's club… have been banished” (The Age, 5 Dec. 2007). Some of these signs were soon replaced by Ms. Gillard herself, who filled the office in turn with memorabilia from her beloved Footscray, an Australian Rules football team. In post-coalitional Australia the exile of the old Menzies’ desk and a pair of Chesterfield sofas works alongside the withdrawal of troops from Iraq and renewed pledges for military presence in Afghanistan, apologising to stolen generations of Indigenous Australians, the first female Governor General, deputy Prime Minister and then Prime Minister (the last two both Gillard), the repealing of disadvantageous workplace reform, a focus on climate change and global warming (with limited success as stated), a public, mandatory paid maternity leave scheme, changes to the processing and visas of refugees, and the amendments to more than one hundred laws that discriminate against same sex couples by the pre-Gillard, Rudd-led Labor government. The context for these changes was encapsulated in an announcement from Rudd, made in March 2008: Our core organising principle as a Government is equality of opportunity. And advancing people and their opportunities in life, we are a Government which prides itself on being blind to gender, blind to economic background, blind to social background, blind to race, blind to sexuality. (Rudd, “International”) Noting the political possibilities and the political convenience of blindness, this paper navigates the confusing context of post-coalitional Australia, whilst proffering an understanding of some of the cultural forces at work in this age of shifting and unstable alliances. I begin by interrogating the coalitional impulse post 9/11. I do this by connecting public coalitional shifts to the steady withdrawal of support for John Howard’s coalition, and movement away from George Bush’s Coalition of the Willing and the War on Terror. I then draw out a relationship between the rise and fall of such affiliations and recent shifts within government policy affecting same-sex couples, from former Prime Minister Howard’s amendments to The Marriage Act 1961 to the Rudd-Gillard administration’s attention to the discrimination in many Australian laws. Sexual Citizenship and Coalitions Rights and entitlements have always been constructed and managed in ways that live out understandings of biopower and social death (Foucault History; Discipline). The disciplining of bodies, identities and pleasures is so deeply entrenched in government and law that any non-normative claim to rights requires the negotiation of existing structures. Sexual citizenship destabilises the post-coalitional paradigm of Australian politics (one of “equal opportunity” and consensus) by foregrounding the normative biases that similarly transcend partisan politics. Sexual citizenship has been well excavated in critical work from Evans, Berlant, Weeks, Richardson, and Bell and Binnie’s The Sexual Citizen which argues that “many of the current modes of the political articulation of sexual citizenship are marked by compromise; this is inherent in the very notion itself… the twinning of rights with responsibilities in the logic of citizenship is another way of expressing compromise… Every entitlement is freighted with a duty” (2-3). This logic extends to political and economic contexts, where “natural” coalition refers primarily to parties, and in particular those “who have powerful shared interests… make highly valuable trades, or who, as a unit, can extract significant value from others without much risk of being split” (Lax and Sebinius 158). Though the term is always in some way politicised, it need not refer only to partisan, multiparty or multilateral configurations. The subscription to the norms (or normativity) of a certain familial, social, religious, ethnic, or leisure groups is clearly coalitional (as in a home or a front, a club or a team, a committee or a congregation). Although coalition is interrogated in political and social sciences, it is examined frequently in mathematical game theory and behavioural psychology. In the former, as in Axelrod’s The Evolution of Cooperation, it refers to people (or players) who collaborate to successfully pursue their own self-interests, often in the absence of central authority. In behavioural psychology the focus is on group formations and their attendant strategies, biases and discriminations. Experimental psychologists have found “categorizing individuals into two social groups predisposes humans to discriminate… against the outgroup in both allocation of resources and evaluation of conduct” (Kurzban, Tooby and Cosmides 15387). The actions of social organisation (and not unseen individual, supposedly innate impulses) reflect the cultural norms in coalitional attachments – evidenced by the relationship between resources and conduct that unquestioningly grants and protects the rights and entitlements of the larger, heteronormatively aligned “ingroup”. Terror Management Particular attention has been paid to coalitional formations and discriminatory practices in America and the West since September 11, 2001. Terror Management Theory or TMT (Greenberg, Pyszczynski and Solomon) has been the main framework used to explain the post-9/11 reassertion of large group identities along ideological, religious, ethnic and violently nationalistic lines. Psychologists have used “death-related stimuli” to explain coalitional mentalities within the recent contexts of globalised terror. The fear of death that results in discriminatory excesses is referred to as “mortality salience”, with respect to the highly visible aspects of terror that expose people to the possibility of their own death or suffering. Naverette and Fessler find “participants… asked to contemplate their own deaths exhibit increases in positive evaluations of people whose attitudes and values are similar to their own, and derogation of those holding dissimilar views” (299). It was within the climate of post 9/11 “mortality salience” that then Prime Minister John Howard set out to change The Marriage Act 1961 and the Family Law Act 1975. In 2004, the Government modified the Marriage Act to eliminate flexibility with respect to the definition of marriage. Agitation for gay marriage was not as noticeable in Australia as it was in the U.S where Bush publicly rejected it, and the UK where the Civil Union Act 2004 had just been passed. Following Bush, Howard’s “queer moral panic” seemed the perfect decoy for the increased scrutiny of Australia’s involvement in the Iraq war. Howard’s changes included outlawing adoption for same-sex couples, and no recognition for legal same-sex marriages performed in other countries. The centrepiece was the wording of The Marriage Amendment Act 2004, with marriage now defined as a union “between a man and a woman to the exclusion of all others”. The legislation was referred to by the Australian Greens Senator Bob Brown as “hateful”, “the marriage discrimination act” and the “straight Australia policy” (Commonwealth 26556). The Labor Party, in opposition, allowed the changes to pass (in spite of vocal protests from one member) by concluding the legal status of same-sex relations was in no way affected, seemingly missing (in addition to the obvious symbolic and physical discrimination) the equation of same-sex recognition with terror, terrorism and death. Non-normative sexual citizenship was deployed as yet another form of “mortality salience”, made explicit in Howard’s description of the changes as necessary in protecting the sanctity of the “bedrock institution” of marriage and, wait for it, “providing for the survival of the species” (Knight, 5 Aug. 2003). So two things seem to be happening here: the first is that when confronted with the possibility of their own death (either through terrorism or gay marriage) people value those who are most like them, joining to devalue those who aren’t; the second is that the worldview (the larger religious, political, social perspectives to which people subscribe) becomes protection from the potential death that terror/queerness represents. Coalition of the (Un)willing Yet, if contemporary coalitions are formed through fear of death or species survival, how, for example, might these explain the various forms of risk-taking behaviours exhibited within Western democracies targeted by such terrors? Navarette and Fessler (309) argue that “affiliation defences are triggered by a wider variety of threats” than “existential anxiety” and that worldviews are “in turn are reliant on ‘normative conformity’” (308) or “normative bias” for social benefits and social inclusions, because “a normative orientation” demonstrates allegiance to the ingroup (308-9). Coalitions are founded in conformity to particular sets of norms, values, codes or belief systems. They are responses to adaptive challenges, particularly since September 11, not simply to death but more broadly to change. In troubled times, coalitions restore a shared sense of predictability. In Howard’s case, he seemed to say, “the War in Iraq is tricky but we have a bigger (same-sex) threat to deal with right now. So trust me on both fronts”. Coalitional change as reflective of adaptive responses thus serves the critical location of subsequent shifts in public support. Before and since September 11 Australians were beginning to distinguish between moderation and extremism, between Christian fundamentalism and productive forms of nationalism. Howard’s unwavering commitment to the American-led war in Iraq saw Australia become a member of another coalition: the Coalition of the Willing, a post 1990s term used to describe militaristic or humanitarian interventions in certain parts of the world by groups of countries. Howard (in Pauly and Lansford 70) committed Australia to America’s fight but also to “civilization's fight… of all who believe in progress and pluralism, tolerance and freedom”. Although Bush claimed an international balance of power and influence within the coalition (94), some countries refused to participate, many quickly withdrew, and many who signed did not even have troops. In Australia, the war was never particularly popular. In 2003, forty-two legal experts found the war contravened International Law as well as United Nations and Geneva conventions (Sydney Morning Herald 26 Feb. 2003). After the immeasurable loss of Iraqi life, and as the bodies of young American soldiers (and the occasional non-American) began to pile up, the official term “coalition of the willing” was quietly abandoned by the White House in January of 2005, replaced by a “smaller roster of 28 countries with troops in Iraq” (ABC News Online 22 Jan. 2005). The coalition and its larger war on terror placed John Howard within the context of coalitional confusion, that when combined with the domestic effects of economic and social policy, proved politically fatal. The problem was the unclear constitution of available coalitional configurations. Howard’s continued support of Bush and the war in Iraq compounded with rising interest rates, industrial relations reform and a seriously uncool approach to the environment and social inclusion, to shift perceptions of him from father of the nation to dangerous, dithery and disconnected old man. Post-Coalitional Change In contrast, before being elected Kevin Rudd sought to reframe Australian coalitional relationships. In 2006, he positions the Australian-United States alliance outside of the notion of military action and Western territorial integrity. In Rudd-speak the Howard-Bush-Blair “coalition of the willing” becomes F. Scott Fitzgerald’s “willingness of the heart”. The term coalition was replaced by terms such as dialogue and affiliation (Rudd, “Friends”). Since the 2007 election, Rudd moved quickly to distance himself from the agenda of the coalition government that preceded him, proposing changes in the spirit of “blindness” toward marginality and sexuality. “Fix-it-all” Rudd as he was christened (Sydney Morning Herald 29 Sep. 2008) and his Labor government began to confront the legacies of colonial history, industrial relations, refugee detention and climate change – by apologising to Aboriginal people, timetabling the withdrawal from Iraq, abolishing the employee bargaining system Workchoices, giving instant visas and lessening detention time for refugees, and signing the Kyoto Protocol agreeing (at least in principle) to reduce green house gas emissions. As stated earlier, post-coalitional Australia is not simply talking about sudden change but an extension and a confusion of what has gone on before (so that the term resembles postcolonial, poststructural and postmodern because it carries the practices and effects of the original term within it). The post-coalitional is still coalitional to the extent that we must ask: what remains the same in the midst of such visible changes? An American focus in international affairs, a Christian platform for social policy, an absence of financial compensation for the Aboriginal Australians who received such an eloquent apology, the lack of coherent and productive outcomes in the areas of asylum and climate change, and an impenetrable resistance to the idea of same-sex marriage are just some of the ways in which these new governments continue on from the previous one. The Rudd-Gillard government’s dealings with gay law reform and gay marriage exemplify the post-coalitional condition. Emulating Christ’s relationship to “the marginalised and the oppressed”, and with Gillard at his side, Rudd understandings of the Christian Gospel as a “social gospel” (Rudd, “Faith”; see also Randell-Moon) to table changes to laws discriminating against gay couples – guaranteeing hospital visits, social security benefits and access to superannuation, resembling de-facto hetero relationships but modelled on the administering and registration of relationships, or on tax laws that speak primarily to relations of financial dependence – with particular reference to children. The changes are based on the report, Same Sex, Same Entitlements (HREOC) that argues for the social competence of queer folk, with respect to money, property and reproduction. They speak the language of an equitable economics; one that still leaves healthy and childless couples with limited recognition and advantage but increased financial obligation. Unable to marry in Australia, same-sex couples are no longer single for taxation purposes, but are now simultaneously subject to forms of tax/income auditing and governmental revenue collection should either same-sex partner require assistance from social security as if they were married. Heteronormative Coalition Queer citizens can quietly stake their economic claims and in most states discreetly sign their names on a register before becoming invisible again. Mardi Gras happens but once a year after all. On the topic of gay marriage Rudd and Gillard have deferred to past policy and to the immoveable nature of the law (and to Howard’s particular changes to marriage law). That same respect is not extended to laws passed by Howard on industrial relations or border control. In spite of finding no gospel references to Jesus the Nazarene “expressly preaching against homosexuality” (Rudd, “Faith”), and pre-election promises that territories could govern themselves with respect to same sex partnerships, the Rudd-Gillard government in 2008 pressured the ACT to reduce its proposed partnership legislation to that of a relationship register like the ones in Tasmania and Victoria, and explicitly demanded that there be absolutely no ceremony – no mimicking of the real deal, of the larger, heterosexual citizens’ “ingroup”. Likewise, with respect to the reintroduction of same-sex marriage legislation by Greens senator Sarah Hanson Young in September 2010, Gillard has so far refused a conscience vote on the issue and restated the “marriage is between a man and a woman” rhetoric of her predecessors (Topsfield, 30 Sep. 2010). At the same time, she has agreed to conscience votes on euthanasia and openly declared bi-partisan (with the federal opposition) support for the war in Afghanistan. We see now, from Howard to Rudd and now Gillard, that there are some coalitions that override political differences. As psychologists have noted, “if the social benefits of norm adherence are the ultimate cause of the individual’s subscription to worldviews, then the focus and salience of a given individual’s ideology can be expected to vary as a function of their need to ally themselves with relevant others” (Navarette and Fessler 307). Where Howard invoked the “Judaeo-Christian tradition”, Rudd chose to cite a “Christian ethical framework” (Rudd, “Faith”), that saw him and Gillard end up in exactly the same place: same sex relationships should be reduced to that of medical care or financial dependence; that a public ceremony marking relationship recognition somehow equates to “mimicking” the already performative and symbolic heterosexual institution of marriage and the associated romantic and familial arrangements. Conclusion Post-coalitional Australia refers to the state of confusion borne of a new politics of equality and change. The shift in Australia from conservative to mildly socialist government(s) is not as sudden as Howard’s 2007 federal loss or as short-lived as Gillard’s hung parliament might respectively suggest. Whilst allegiance shifts, political parties find support is reliant on persistence as much as it is on change – they decide how to buffer and bolster the same coalitions (ones that continue to privilege white settlement, Christian belief systems, heteronormative familial and symbolic practices), but also how to practice policy and social responsibility in a different way. Rudd’s and Gillard’s arguments against the mimicry of heterosexual symbolism and the ceremonial validation of same-sex partnerships imply there is one originary form of conduct and an associated sacred set of symbols reserved for that larger ingroup. Like Howard before them, these post-coalitional leaders fail to recognise, as Butler eloquently argues, “gay is to straight not as copy is to original, but as copy is to copy” (31). To make claims to status and entitlements that invoke the messiness of non-normative sex acts and romantic attachments necessarily requires the negotiation of heteronormative coalitional bias (and in some ways a reinforcement of this social power). As Bell and Binnie have rightly observed, “that’s what the hard choices facing the sexual citizen are: the push towards rights claims that make dissident sexualities fit into heterosexual culture, by demanding equality and recognition, versus the demand to reject settling for heteronormativity” (141). The new Australian political “blindness” toward discrimination produces positive outcomes whilst it explicitly reanimates the histories of oppression it seeks to redress. The New South Wales parliament recently voted to allow same-sex adoption with the proviso that concerned parties could choose not to adopt to gay couples. The Tasmanian government voted to recognise same-sex marriages and unions from outside Australia, in the absence of same-sex marriage beyond the current registration arrangements in its own state. In post-coalitional Australia the issue of same-sex partnership recognition pits parties and allegiances against each other and against themselves from within (inside Gillard’s “rainbow coalition” the Rainbow ALP group now unites gay people within the government’s own party). Gillard has hinted any new proposed legislation regarding same-sex marriage may not even come before parliament for debate, as it deals with real business. Perhaps the answer lies over the rainbow (coalition). As the saying goes, “there are none so blind as those that will not see”. References ABC News Online. “Whitehouse Scraps Coalition of the Willing List.” 22 Jan. 2005. 1 July 2007 ‹http://www.abc.net.au/news/newsitems/200501/s1286872.htm›. Axelrod, Robert. The Evolution of Cooperation. New York: Basic Books, 1984. 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