Littérature scientifique sur le sujet « Home-cage testing »

AbstractSingle housing is believed to be chronically stressful and to have a negative impact on welfare and cognition in rats (Rattus norvegicus). However, single housing does not consistently evoke stress-like responses nor does it consistently impair cognitive performance. In an experiment in which all cages were separated by an opaque barrier, single- and pair-housed pigmented (dark-eyed) rats performed equally in a cognitive test and displayed similar levels of anxiety during testing. Additionally, bar biting in the home cage did not differ between the two groups. Stress levels both during cognitive testing and in the home cage were higher than those we have previously reported when rats were housed without opaque barriers between the cages. We conclude that visual interactions between rats in different cages may be of sufficient significance that single housing in a cage with a view to neighbouring rats and to the rest of the laboratory holding room may be preferable to pair housing in a cage without this view.

The cognitive bias test is used to measure the emotional state of animals with regard to future expectations. Thus, the test offers a unique possibility to assess animal welfare with regard to housing and testing conditions of laboratory animals. So far, however, performing such a test is time-consuming and requires the presence of an experimenter. Therefore, we developed an automated and home-cage based cognitive bias test based on the IntelliCage system. We present several developmental steps to improve the experimental design leading to a successful measurement of cognitive bias in group-housed female C57BL/6J mice. The automated and home-cage based test design allows to obtain individual data from group-housed mice, to test the mice in their familiar environment, and during their active phase. By connecting the test-cage to the home-cage via a gating system, the mice participated in the test on a self-chosen schedule, indicating high motivation to actively participate in the experiment. We propose that this should have a positive effect on the animals themselves as well as on the data. Unexpectedly, the mice showed an optimistic cognitive bias after enrichment was removed and additional restraining. An optimistic expectation of the future as a consequence of worsening environmental conditions, however, can also be interpreted as an active coping strategy in which a potential profit is sought to be maximized through a higher willingness to take risks.

Nervous system impairment is prominent among signs of chemical toxicity in humans and animals, yet evaluation of behavioral and neurologic responses is seldom included in premarket screening. The sensitivity and validity of automatically recorded rodent locomotor activity, whether inside or outside of the home cage, justifies its inclusion in first-tier testing. Home cage behaviors are studied in the toxicologic laboratory using quantitative techniques from behavioral neuroscience. A practical, noninvasive, automated system was developed and validated at New York University, in accord with Federal guidelines for testing neurotoxicity. Effects of neurotoxicants on motor activity, eating, drinking, and the daily cycle of rest-activity indicate sensitivity to a variety of chemicals as well as new avenues to the understanding of mechanisms of toxicity. The rat's pattern of nocturnal activity is particularly sensitive to neurotoxicants and thus deserves additional attention. The coefficient of variability of various end points did not correlate with sensitivity to toxicants. This underscores the need for behavioral data to supplement theoretical considerations in test selection. The system's advantages are economy, high data capacity, humaneness, accessible and well-known end points, widely available equipment, automation, and the potential for direct comparisons of several different animal species.

In response to present and anticipated regulatory needs for routine screening of pharmaceuticals for assessment of their neurotoxic potential, a primary tier screen for rodents, consisting of a functional observational battery (FOB) and an automated test of motor activity, has been developed at Searle. Additionally, an FOB for dogs currently is being developed. The rodent FOB assess such functions as home cage and open field activity, stimulus reactivity, and neuromuscular function. The dog FOB emphasizes evaluation of gait, postural reactions, and reflex function. The strategy taken has been to incorporate the primary rodent tier screen into repeated dose preclinical studies. Positive findings would trigger a secondary tier of testing, which would involve the use of more complex and integrated tests of neurobehavioral function. The methodologies for both rodent and nonrodent primary tier screens, validation study results, and the scientific criteria that would trigger secondary tier testing are discussed.

The aim of this study was to develop and refine a heterologous mouse model of endometriosis-associated pain in which non-evoked responses, more relevant to the patient experience, were evaluated. Immunodeficient female mice (N = 24) were each implanted with four endometriotic human lesions (N = 12) or control tissue fat (N = 12) on the abdominal wall using tissue glue. Evoked pain responses were measured biweekly using von Frey filaments. Non-evoked responses were recorded weekly for 8 weeks using a home cage analysis (HCA). Endpoints were distance traveled, social proximity, time spent in the center vs. outer areas of the cage, drinking, and climbing. Significant differences between groups for von Frey response, climbing, and drinking were detected on days 14, 21, and 35 post implanting surgery, respectively, and sustained for the duration of the experiment. In conclusion, a heterologous mouse model of endometriosis-associated evoked a non-evoked pain was developed to improve the relevance of preclinical models to patient experience as a platform for drug testing.

Abstract Aims This study aimed to gain methodological knowledge about quantification of mechanical nociceptive thresholds in pigs stimulated on the hind legs. Methods Thirty-two castrated male pigs were used, weighing 50–60kg, 16 weeks of age and housed in standard pens (4.40m×4.40m) with ad libitum access to water and feed. Mechanical nociceptive testing (4 stimulations/pig) was done by an electronic von Frey anesthesiometer (IITC Life Science Inc., CA) with a rigid, hollow plastic tip (cut-off: 1000 gf) and an area of 0.3 mm2. Stimulations targeted caudal aspects of the metatarsus while the pigs were restrained in a cage measuring 35cm×40cm (length×width). During the last 3d before nociceptive testing, half of the pigs were habituated to the experimental set-up twice daily. Results Across the three days, the habituation procedure led to a reduction in time required to approach and release the pigs from the home pen (P<0.05) and to increased acceptance of the confinement (P<0.01). The habituated animals had a lower mechanical nociceptive threshold (median: 495gf (302–675) vs 745gf (479–1000); P<0.05), and a decreased occurrence of censored observations (0 vs 25%; P<0.05) compared to animals tested without habituation. Conclusions The present experiment focussed on methodological aspects of hand-held tests of mechanical nociceptive thresholds in pigs. The results show that the pigs responded to a 3-day habituation regime by increased ease of handling and tolerance of being confined in a test cage. In addition, habituation to the test environment and handling led to reduced mechanical nociceptive thresholds as well as a lowered proportion of censored observations. The current results reiterate the value of habituation in research involving animal behaviour. Further characterization of the methodology is needed to allow its application in the evaluation of clinical conditions in pigs.

Rodent tests of function have advanced our understanding of movement, largely through the human training and testing and manual assessment. Tools such as reaching and grasping of a food pellet have been widely adopted because they are effective and simple to use. However, these tools are time-consuming, subjective, and often qualitative. Automation of training, testing, and assessment has the potential to increase efficiency while ensuring tasks are objective and quantitative. We detail new methods for automating rodent forelimb tests, including the use of pellet dispensers, sensors, computer vision, and home cage systems. We argue that limitations in existing forelimb tasks are driving the innovations in automated systems. We further argue that automated tasks partially address these limitations, and we outline necessary precautions and remaining challenges when adopting these types of tasks. Finally, we suggest attributes of future automated rodent assessment tools that can enable widespread adoption and help us better understand forelimb function in health and disease.

With the growing awareness of the neurological effects of many environmental chemicals, there is considerable emphasis being placed on the detection of neurotoxic potential at the screening, or first-tier, level of testing. We have developed a neurobehavioral screening battery consisting of a functional observational battery (FOB) and an automated measure of motor activity which can be incorporated into neuropathological studies as well as general toxicity assessments of new and existing chemicals in rats. This approach has been recommended by several expert national and international panels, and recently has been recommended by the U.S. Environmental Protection Agency for testing pesticides and industrial chemicals. The FOB consists of a series of home-cage, open-field, and interactive assessments of the rat's behavior and neurological functions. Motor activity provides an objective apical measure of the rat's neurobehavioral function. In order to assess validity, sensitivity, and specificity, we have utilized these test methods to determine dose-response and time-course characteristics of a wide variety of chemicals including pesticides, metals, solvents, and industrial compounds. We currently are developing approaches to provide profiles of effect for different types of neurotoxicants, which can then be used to make decisions concerning neurotoxic potential and provide direction for more in-depth, second-tier testing.

Impulsivity, risk proneness, and poor decision-making are common behavioural symptoms observed in impulse-control disorders, a neuropsychiatric category including attention-deficit/hyperactivity disorder (ADHD) as well as pathological gambling (PG). ADHD, affecting about 3-5% of children, is characterized by traits of inattention, impulsivity, and motor hyperactivity. PG, affecting 0.2-5.3% of adults and 3.5-8.0% of adolescents, is highly comorbid with a range of addictive disorders and is frequently observed in ADHD adolescents and adults. Interest is rising for animal modelling of impaired behavioural inhibition: in order to test the lack of self-control abilities and/or impulsive decision-making, many operant paradigms have been developed, involving a choice with delayed and/or uncertain reinforcers. These choice-based operant tasks, which assess the balance between motivational drives and inhibitory self-control, are extremely useful for investigating reward-discounting processes and their modulation by 5-HT-targeting manipulations. The present thesis is thus focused on the modelling, in laboratory rats, of key symptoms like impulsivity and gambling proneness. Specifically, the first part (chapters 2 and 3) includes a methodological refinement of the operant tasks used, such as Intolerance-to-Delay (ID) and Probabilistic-Delivery (PD) tasks, whereas the second part (chapters 4 and 5) relates to experimental manipulations of the serotonergic influence on these symptoms”. In chapter 2, we report about the marked impact exerted by duration of post-reward timeout (TO) and daily session length (SL) on impulsive choice and gambling proneness in the ID and PD tasks respectively. In chapter 3, we discuss about the role of different methodological improvements in the PD task, implemented (on both the paradigm and the apparatus) to allow testing of adolescent rats in the home-cage, while socially living and within the limited span of this developmental phase. In the fourth chapter, serotonin (5-HT) levels have been manipulated by means of a diet deficient in its precursor, tryptophan (TRP); in the fifth chapter, serotonin transporter (SERT) levels within the hippocampus of rats have been altered through genetic engineering techniques that allow to modulate in-vivo gene expression in specific brain areas. The findings reported in chapter 4 show that TRP depletion leads to changes in behavioural responses related to decision-making as well as a gambling proneness. In chapter 5, we demonstrated that a partial silencing of the SERT-encoding gene is effective in inducing alterations which are consistent with the symptoms of hyperactivity and impulsivity. In conclusion, due to the complexity of human studies, preclinical investigations in rodent models are necessary for a deeper understanding of ADHD-like symptoms, their neurobiological determinants and their possible modulation by serotonergic manipulations. Further research is essential to increase our knowledge of the psychobiology of ADHD and PG as well as other disorders in which the inhibitory control is compromised.

We describe the design and testing of an implantable miniature infusion pump that uses a rechargeable battery as a power source. This design includes a receiver printed coil that allows inductive power transfer from a transmitter coil wound around a 20 cm diameter charging unit and a frequency-gated optical sensor that allows activation of the pump at a distance using pulses of infrared light. This mini pump can be charged in the home cage by inductive power transfer, and then operates independently from its power link in freely moving animals.