Behavior In Laboratory Animals Research Articles

Synergistic anxiolytic efficacy exploring the combined effects of diazepam and zinc chloride in wistar albino rats.

Combinations of medications are frequently employed when their effects are similar. Beyond aiding in the reduction of medication dosages, this approach may yield additional positive outcomes. Studies have shown that zinc can mitigate anxiety-related behavior in laboratory animals. This study aimed to investigate the potential stabilizing effects of zinc chloride and diazepam in Wistar albino rats.Five groups, each comprising six animals. Test groups included two combinations of zinc chloride and diazepam, each with two different doses of diazepam (1 and 2 mg/kg) and 10 mg/kg of zinc chloride. Four established anxiety models-the Elevated Plus Maze (EPM), the hole board, the light and dark box, and the mirror chamber-were employed to assess the anxiolytic effects. The combination of zinc chloride and diazepam proved to be more effective than the individual doses of zinc chloride and diazepam, indicating enhanced anxiolytic effects.

Effect Sizes of Cognitive and Locomotive Behavior Tests in the 5XFAD-J Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by the accumulation of amyloid β (Aβ) plaques in the brain, leading to cognitive impairment and other clinical symptoms. The 5XFAD mouse model is commonly used in AD research because it expresses five human transgenes that result in the accumulation of Aβ plaques and cognitive decline at a relatively early age. Behavioral experiments are frequently conducted using this model; however, the effect size has not yet been reported. In this study, we examined basic cognition and locomotion in 5XFAD mice with a C57BL6/J background (5XFAD-J) at 6 months of age, a period in which impairments of cognitive function and locomotion are commonly observed. We analyzed the effect sizes of cognitive and locomotive experiments in the 5XFAD mice compared with those in the wild-type mice. Our results suggest that for long-term memory analysis, the novel object recognition test (p = 0.013, effect size 1.24) required a sample size of at least 12 to obtain meaningful results. Moreover, analysis of general locomotion over total distance with the Laboratory Animal Behavior Observation, Registration and Analysis System (LABORAS) test during the dark phase (p = 0.007, effect size -1.37) needed a sample size of 10 for a statistical power (1-β) of 0.8. In conclusion, we can conduct more ethical and scientifically rigorous animal experiments using 5XFAD mice based on the effect and sample sizes suggested in this study.

Development of two mouse strains conditionally expressing bright luciferases with distinct emission spectra as new tools for in vivo imaging.

In vivo bioluminescence imaging (BLI) has been an invaluable noninvasive method to visualize molecular and cellular behaviors in laboratory animals. Bioluminescent reporter mice harboring luciferases for general use have been limited to a classical luciferase, Luc2, from Photinus pyralis, and have been extremely powerful for various in vivo studies. However, applicability of reporter mice for in vivo BLI could be further accelerated by increasing light intensity through the use of other luciferases and/or by improving the biodistribution of their substrates in the animal body. Here we created two Cre-dependent reporter mice incorporating luciferases oFluc derived from Pyrocoeli matsumurai and Akaluc, both of which had been reported previously to be brighter than Luc2 when using appropriate substrates; we then tested their bioluminescence in neural tissues and other organs in living mice. When expressed throughout the body, both luciferases emitted an intense yellow (oFluc) or far-red (Akaluc) light easily visible to the naked eye. oFluc and Akaluc were similarly bright in the pancreas for in vivo BLI; however, Akaluc was superior to oFluc for brain imaging, because its substrate, AkaLumine-HCl, was distributed to the brain more efficiently than the oFluc substrate, D-luciferin. We also demonstrated that the lights produced by oFluc and Akaluc were sufficiently spectrally distinct from each other for dual-color imaging in a single living mouse. Taken together, these novel bioluminescent reporter mice are an ideal source of cells with bright bioluminescence and may facilitate in vivo BLI of various tissues/organs for preclinical and biomedical research in combination with a wide variety of Cre-driver mice.

Effect of apparatus characteristics on anxiety-like behavior in young adult and old mice of both sexes assessed by the elevated plus maze assay.

Incidence of anxiety-like disorders in humans has been shown to decrease with aging; however, it is still under debate whether there are similarities in mice, which would support the use of mouse models in understanding the neuronal network changes that regulate anxiety-like behavior in aging. One of the most common tests used to assess anxiety-like behavior in laboratory animals is the elevated plus maze (EPM). Although several variables, such as room brightness and width of the maze arms, have been shown to influence the spontaneous animal behavior during the EPM test, none of these variables have ever been evaluated in aging to understand their possible differential effect on younger and older mice. We therefore decided to investigate the effect of apparatus construction on young adult and old mice of both sexes on EPM test performance. Our results show that distance traveled during the test is the variable that is most affected by apparatus characteristics independent of age and sex. We also found that apparatus construction was key in demonstrating that old mice spent more time and had relatively more entries in the open arms as compared to young mice, suggesting a decrease in anxiety-like behavior with age. Taken together, our data demonstrate that EPM apparatus characteristics dramatically affect test outcome with a wider arm apparatus being more effective in revealing age-dependent changes in anxiety-like behavior, thus, suggesting the use of a wider arm EPM when conducting aging studies in mice.

The influence of flour confectionery products based on flour from light-grain rye and processed products of carrots and beets on the behavioral reactions of laboratory rats

Relevance. In modern conditions, due to the increasing popularity of healthy nutrition, more and more attention is being paid to functional foods that can effectively solve the problem of prevention and treatment of various diseases associated with a deficiency of certain substances. In the production of functional food products, natural biologically active substances of plant origin are used, which have an impact not only on health, but also on the behavioral reactions of laboratory animals.Methods. The animals of the control group were kept on a standard diet, consisting of a mixture of cereals in accordance with the recommendations. In the experimental groups, the feed of the main diet was replaced with experimental functional flour confectionery products developed by the authors of the work, and with products sold in retail stores. Behavioral features of laboratory rats were evaluated in the «Open Field». The reliability of the differences was determined by nonparametric statistics (at p < 0.05).Results. The results indicate a positive effect of a diet containing flour confectionery products based on flour from light rye grain with vegetable processing products on the behavioral reactions of laboratory rats. Regular consumption of flour confectionery products based on flour from light-grain rye and processed products of carrot and beet root vegetables in the dining room increases the active-search and reduces the passive-defensive components of the behavior of laboratory animals.

Validation of a system for automatic quantitative analysis of laboratory mice behavior based on locomotor pose

Automatic recognition and accurate quantitative analysis of rodent behavior play an important role in brain neuroscience, pharmacological and toxicological. Currently, most behavior recognition systems used in experiments mainly focus on the indirect measurements of animal movement trajectories, while neglecting the changes of animal body pose that can indicate more psychological factors. Thus, this paper developed and validated an hourglass network-based behavioral quantification system (HNBQ), which uses a combination of body pose and movement parameters to quantify the activity of mice in an enclosed experimental chamber. In addition, The HNBQ was employed to record behavioral abnormalities of head scanning in the presence of food gradients in open field test (OFT). The results proved that the HNBQ in the new object recognition (NOR) experiment was highly correlated with the scores of manual observers during the latent exploration period and the cumulative exploration time. Moreover, in the OFT, HNBQ was able to capture the subtle differences in head scanning behavior of mice in the gradient experimental groups. Satisfactory results support that the combination of body pose and motor parameters can regard as a new alternative approach for quantification of animal behavior in laboratory.

Batatasin III, a Constituent of Dendrobium scabrilingue, Improves Murine Pain-like Behaviors with a Favorable CNS Safety Profile.

Batatasin III is a stilbenoid compound present in a wide variety of Dendrobium species. Although the pharmacological efficacy of batatasin III has been reported in several disease models, its antinociceptive efficacy and central nervous system (CNS) side effects remain unknown. Thus, this study examined the effects of batatasin III on pain-like behaviors in mouse models of formalin- and lipopolysaccharide (LPS)-induced inflammatory pain. The results revealed a significant antinociceptive effect of batatasin III in both models, as 50 mg/kg batatasin III elicited comparable antinociception as 10 mg/kg indomethacin. Further, the anti-inflammatory effect of batatasin III was assessed in LPS-induced RAW 264.7 macrophages and BV-2 microglial cells. The compound significantly reduced the levels of inflammatory mediators (nitric oxide, TNF-α, and IL-6) in LPS-stimulated cells in a concentration-dependent manner. Following efficacy evaluations, the potential CNS side effects of batatasin III were evaluated using the rotarod test and the Laboratory Animal Behavior Observation, Registration, and Analysis System. Batatasin III-treated mice exhibited comparable forced, spontaneous, and general locomotive behaviors to vehicle-treated mice, indicating no potential CNS side effects. Overall, this study demonstrated the preclinical antinociceptive efficacy and CNS safety of batatasin III, suggesting its potential role in the development of new analgesics.

Perfluorooctanoate and perfluorooctane sulfonate in umbilical cord blood and child cognitive development: Hamamatsu Birth Cohort for Mothers and Children (HBC Study).

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been shown to affect offspring behaviors in laboratory animals. Several epidemiological studies investigated associations between prenatal PFAS exposure and child neurodevelopment, but results were inconclusive. We examined associations between cord blood concentrations of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) and cognitive development in children from 4 to 40months of age. This study included 598 mother-child pairs who participated in the Hamamatsu Birth Cohort Study for Mothers and Children (HBC Study), a prospective birth cohort study in Japan. PFOA and PFOS were quantified in cord blood. The Mullen Scales of Early Learning (MSEL) was used to assess child cognitive function at 4, 6, 10, 14, 18, 24, 32, and 40months of age. For each of log 2-transformed PFOA and PFOS concentrations, we examined: 1) associations with the scores of MSEL Early Learning Composite (Composite) and four subscales (Fine Motor, Visual Reception, Receptive Language, Expressive Language) at each assessment time point; and 2) associations with longitudinal changes in the Composite and subscale scores. MSEL Composite scores were inversely associated with PFOA at 18months of age (per 2-fold increase in concentration: β=-2.23, 95% CI: -3.91, -0.56), but not at other ages. When accounting for changes in scores from 4 to 40months of age, PFOA and PFOS were positively associated with Composite as well as Receptive and Expressive Language scores. Child's sex modified associations between PFOA and Composite scores at 14, 18, and 40months and those between PFOS and Composite scores at 14months, showing negative associations among females. In this study, cord blood PFOA and PFOS concentrations showed mixed associations with child cognitive functions at specific age but had positive associations with longitudinal changes in cognitive development from 4 to 40months of age.

Psycho-Behavioural Changes in Dogs Treated with Corticosteroids: A Clinical Behaviour Perspective

Simple SummaryCorticosteroids hormones are central to stress responses and, along with other hormones and neurotransmitters, contribute to the onset of physiological and behavioural changes aimed at helping the animal cope with anticipated demand. Both the human and animal literature suggest that exposure to systemic exogenous corticosteroid treatments can be associated with negative emotional states. In this paper, the potential behavioural effects of exogenous corticosteroid treatment on dogs and other species are discussed to show why consideration should be given to this matter when prescribing these drugs.Arousal and distress are often important factors in problematic behaviours, and endogenous corticosteroids are important mediators in the associated stress responses. Exogenous corticosteroid treatments have been reported to change behaviour in human patients and laboratory animals, with similar changes also noted in pet dogs. These behaviours not only potentially adversely impact the welfare of the dogs, but also the quality of life of their owners. Indeed, corticosteroids can bias sensitivity towards aversion in dogs. A decrease in behaviours associated with positive affective states, such as play and exploratory behaviours, together with an increase in aggression and barking have also been described in dogs. According to the available literature, human patients with pre-existing psychiatric disorders are more at risk of developing behavioural side effects due to corticosteroid treatments. It is reasonable to consider that the same may happen in dogs with pre-existing behavioural problems. In this paper, the possible behavioural side effects of exogenous corticosteroids are summarised to help inform and support veterinarians prescribing these drugs.

Development and application of animal behavior analysis system using video images

There is an urgent need for the development of therapeutic drugs for central nervous system (CNS) diseases, such as depression, dementia, and pain. Behavioral analysis of animal disease models is indispensable for the pathological investigation and drug evaluation of these diseases. However, we do not know whether laboratory animals, such as mice and rats, represent depression, anxiety, and congenital disorders similar to humans. In addition, we do not know how to evaluate their detailed expressions. In the evaluation of various disease models, including CNS diseases, the reproducibility and objectivity of animal experiments and their extrapolation to human beings is always an issue. To address these questions and issues, we need to establish a new evaluation system for experimental animals. In the last decade, the development of technologies for image acquisition and analysis has advanced dramatically, accompanied by an increase in computer processing speed. Various technologies have been developed to analyze human behavior and emotions. These technologies can also be applied to the analysis of animal behavior and emotions. We developed a system to assess the behavior of laboratory animals using video analysis technologies and artificial intelligence. In this review, we introduce technologies that enable the identification of body feature points and behavior and individuals of mice and rats in their home cages. In addition, we discuss the possibility of developing and applying new technologies that will lead to breakthroughs in new drug development.

The influence of glyprolins on the behavior of laboratory animals under experimental hyperthyroidism

This study aimed to determine the peculiarities of behavioral reactions and psychoemotional status of laboratory animals in experimental hyperthyroidism conditions against the background of introducing peptides of glyproline series (selank and tripeptide Pro-Gly-Pro). All experiments were conducted on white non-linear male rats, which were divided into groups consisting of 10 individuals. The first group consisted of control rats that received intraperitoneal water for injection in equi-volume. The second group consisted of individuals with experimental hyperthyroidism modeled by intragastric administration of L-thyroxine Berlin-Chemi Germany) at 150 mcg/kg/day for 21 days. The third and fourth groups were animals with a hyperthyroidism model and received intraperitoneal Selank and Pro-Gly-Pro at 200 mcg/kg/day for 21 days after the hyperthyroidism model development. The behavioral activity determination of laboratory animals was conducted using the Open Field method, which is widely used in the analysis of approximate research activity, locomotive stereotyping, and the emotional reactivity level of rodents. The level of animal anxiety was assessed using the Raised cross-shaped maze method. The study revealed that experimental hyperthyroidism due to the introduction of L-thyroxine is accompanied by an increased level of the anxiety-depressive state in the behavior of male rats. The study on the effects of selank and its structural analog Pro-Gly-Pro on the psychoemotional status of male rats using Open Field and Raised cruciform labyrinth methods revealed that the recovery of the approximate research motor activity of laboratory animals is noted, which indicates the psychomodulatory activity of glyproline neuropeptides, in experimental hyperthyroidism conditions.

Aberrant Lighting Causes Anxiety-like Behavior in Mice but Curcumin Ameliorates the Symptoms.

Simple SummaryIn the present study, we exposed mice to aberrant lighting system and noticed anxiety-like behavior. These symptoms were ameliorated by oral administration of curcumin. The study was carried out on the animals for three weeks in dim light at night (dLAN) and complete darkness (DD), monitoring the body weight, daily food intake, anxiety-like behavior, and expression of the period (PER1) gene. The exposure to dim light at night was found to significantly enhance the anxiety-like behavior and increased the body weight possibly through altered metabolism in mice. In contrast, exposure to DD caused increased anxiety but no significant difference in the body weight. Moreover, the expression of the PER1 gene involved in sleep was also found to be decreased in the aberrant light conditions (dLAN and DD). Although the treatment of curcumin had no effect on the body weight, it had ameliorated the anxiety-like behavior possibly by modulating the expression of the PER1 gene. Thus, the alteration in the light/dark cycle has negative influences on body weight, affecting even the emotional quotient. This study identifies the risk factors associated with aberrant lighting conditions in laboratory animal and ameliorative effects of curcumin. In the modern research field, laboratory animals are constantly kept under artificial lighting conditions. However, recent studies have shown the effect of artificial light on animal behavior and metabolism. In the present study on mice, following three weeks of housing in dim light at night (dLAN; 5lux) and complete darkness (DD; 0lux), we monitored the effect on body weight, daily food intake, anxiety-like behavior by employing the open field test, and expression of the period (PER1) gene. We also studied the effect of oral administration of different concentrations of curcumin (50, 100, and 150 mg/kg) for three weeks in the same mice and monitored these parameters. The exposure to dLAN had significantly increased the anxiety-like behavior and body weight possibly through the altered metabolism in mice, whereas exposure to DD caused increased anxiety but no significant difference in weight gain. Moreover, the expression of the PER1 gene involved in sleep was also found to be decreased in the aberrant light conditions (dLAN and DD). Although the treatment of curcumin had no effect on body weight, it ameliorated the anxiety-like behavior possibly by modulating the expression of the PER1 gene. Thus, alteration in the light/dark cycle had a negative effect on laboratory animals on the body weight and emotions of animals. The present study identifies the risk factors associated with artificial lighting systems on the behavior of laboratory animals and the ameliorative effects of curcumin, with a focus on anxiety-like behavior.

Male–Female Differences in the Effects of Age on Performance Measures Recorded for 23 Hours in Mice

Functional independence is an important aspect of successful aging and differs with age and by sex in humans. Physical performance often declines earlier than other age-associated functional impairments. Rodent models are used to study pharmacological/toxicological effects of human therapies. However, physical outcomes in mice are usually assessed for short periods, with limited information on the influence of age and sex. Here, we investigated how age and sex affected murine physical performance over 23 hours of continuous observation. Young (3 months) and old (22 months) C57BL/6JArc male and female mice were assessed using the Laboratory Animal Behavior Observation, Registration, and Analysis System. Mice were individually housed for recording of distance travelled, mean gait speed, and durations of different physical activities. Compared to young mice of the same sex, old mice travelled significantly shorter distances with slower gait speeds and shorter durations of locomotion, rearing, climbing, and immobility. Older mice groomed significantly more than young mice. Old females reared more during the light cycle than old males. Young females climbed substantially more than young males. Significant Age * Sex interactions were detected for rearing and climbing, whereby an age-related decline was greater in males than in females. Our results suggest that old age reduces exploratory activities and increases grooming in mice. Age-related declines vary between sexes and tend to be greater in males. This noninvasive assessment can be applied to investigate how different interventions affect rodents of different ages and sexes, through the day-night cycle.

Features of the sensitivity of the central nervous system of the organism of experimental animals to the effects of certain psychotropic drugs and their combinations against the background of chronic alcohol intoxication in a chronopharmacological experiment

In a chronopharmacological experiment, the effect of two drugs with psychotropic action in combinations on the behavior of laboratory animals subjected to chronic alcohol intoxication was examined. Against the background of a deprimating agent, a decrease in the threshold of sensitivity to electrical irritation and the duration of an aggressive reaction was revealed; an increase in these indicators was established with a combination of a deprimating drug with an antioxidant. It has been shown that the antioxidant has a desynchronizing effect on the behavioral reactions of laboratory animals for two days, which indicates a pronounced adaptive effect. In the case of using combinations of a deprimating agent with an antioxidant, a decrease in the destruction of the histological structure of the myocardium against the background of chronic alcoholization was established.

Features of the sensitivity of the central nervous system of the organism of experimental animals to the effects of certain psychotropic drugs and their combinations against the background of chronic alcohol intoxication in a chronopharmacological experiment

In a chronopharmacological experiment, the effect of two drugs with psychotropic action in combinations on the behavior of laboratory animals subjected to chronic alcohol intoxication was examined. Against the background of a deprimating agent, a decrease in the threshold of sensitivity to electrical irritation and the duration of an aggressive reaction was revealed; an increase in these indicators was established with a combination of a deprimating drug with an antioxidant. It has been shown that the antioxidant has a desynchronizing effect on the behavioral reactions of laboratory animals for two days, which indicates a pronounced adaptive effect. In the case of using combinations of a deprimating agent with an antioxidant, a decrease in the destruction of the histological structure of the myocardium against the background of chronic alcoholization was established.

Does Pain at an Earlier Stage of Chondropathy Protect Female Mice Against Structural Progression After Surgically Induced Osteoarthritis?

Female C57BL/6 mice exhibit less severe chondropathy than male mice. This study was undertaken to test the robustness of this observation and explore underlying mechanisms. Osteoarthritis was induced in male and female C57BL/6 or DBA/1 mice (n = 6-15 per group) by destabilization of the medial meniscus (DMM) or partial meniscectomy (PMX). Some mice were ovariectomized (OVX) (n = 30). In vivo repair after focal cartilage defect or joint immobilization (sciatic neurectomy) following DMM was assessed. Histologic analysis, evaluation of gene expression in whole knees, and behavioral analysis using Laboratory Animal Behavior Observation Registration and Analysis System (LABORAS) and Linton incapacitance testing (n = 7-10 mice per group) were performed. Female mice displayed less severe chondropathy (20-75% reduction) across both strains and after both surgeries. Activity levels after PMX were similar for male and female mice. Some repair-associated genes were increased in female mouse joints after surgery, but no repair differences were evident in vivo. Despite reduced chondropathy, female mice developed pain-like behavior at the same time as male mice. At the time of established pain-like behavior (10 weeks after PMX), pain-associated genes were significantly up-regulated in female mice, including Gdnf (mean ± SEM fold change 2.54 ± 0.30), Nrtn (6.71 ± 1.24), Ntf3 (1.92 ± 0.27), and Ntf5 (2.89 ± 0.48) (P < 0.01, P < 0.01, P < 0.05, and P < 0.001, respectively, versus male mice). Inflammatory genes were not regulated in painful joints in mice of either sex. We confirm strong structural joint protection in female mice that is not due to activity or intrinsic repair differences. Female mice develop pain at the same time as males, but induce a distinct set of neurotrophins. We speculate that heightened pain sensitivity in female mice protects the joint by preventing overuse.

'Reinventing the wheel' to advance the development of pain therapeutics.

Chronic pain affects approximately one-third of the population worldwide. The primary goal of animal research is to understand the neural mechanisms underlying pain so better treatments can be developed. Despite an enormous investment in time and money, almost no novel treatments for pain have been developed. There are many factors that contribute to this lack of translation in drug development. The mismatch between the goals of drug development in animals (inhibition of pain-evoked responses) and treatment in humans (restoration of function) is a major problem. To solve this problem, a number of pain-depressed behavioral tests have been developed to assess changes in normal behavior in laboratory animals. The use of home cage wheel running as a pain assessment tool is especially useful in that it is easy to use, provides an objective measurement of the magnitude and duration of pain, and is a clinically relevant method to screen novel drugs. Pain depresses activity in humans and animals, and effective analgesic treatments restore activity. Unlike traditional pain-evoked tests (e.g., hot plate, tail flick, von Frey test), restoration of home cage wheel running evaluates treatments for both antinociceptive efficacy and the absence of disruptive side effects (e.g., sedation, paralysis, nausea). This article reviews the literature using wheel running to assess pain and makes the case for home cage wheel running as an effective and clinically relevant method to screen novel analgesics for therapeutic potential.

Nociceptive behavioural assessments in mouse models of temporomandibular joint disorders

Orofacial pain or tenderness is a primary symptom associated with temporomandibular joint (TMJ) disorders (TMDs). To understand the pathological mechanisms underlying TMDs, several mouse models have been developed, including mechanical stimulus-induced TMD and genetic mouse models. However, a lack of feasible approaches for assessing TMD-related nociceptive behaviours in the orofacial region of mice has hindered the in-depth study of TMD-associated mechanisms. This study aimed to explore modifications of three existing methods to analyse nociceptive behaviours using two TMD mouse models: (1) mechanical allodynia was tested using von Frey filaments in the mouse TMJ region by placing mice in specially designed chambers; (2) bite force was measured using the Economical Load and Force (ELF) system; and (3) spontaneous feeding behaviour tests, including eating duration and frequency, were analysed using the Laboratory Animal Behaviour Observation Registration and Analysis System (LABORAS). We successfully assessed changes in nociceptive behaviours in two TMD mouse models, a unilateral anterior crossbite (UAC)-induced TMD mouse model and a β-catenin conditional activation mouse model. We found that the UAC model and β-catenin conditional activation mouse model were significantly associated with signs of increased mechanical allodynia, lower bite force, and decreased spontaneous feeding behaviour, indicating manifestations of TMD. These behavioural changes were consistent with the cartilage degradation phenotype observed in these mouse models. Our studies have shown reliable methods to analyse nociceptive behaviours in mice and may indicate that these methods are valid to assess signs of TMD in mice.

Effects of Ketamine on Rodent Fear Memory.

Ketamine, a multimodal anesthetic drug, has become increasingly popular in the treatment of pain following traumatic injury as well as treatment-resistant major depressive disorders. However, the psychological impact of this dissociative medication on the development of stress-related disorders such as post-traumatic stress disorder (PTSD) remains controversial. To address these concerns, preclinical studies have investigated the effects of ketamine administration on fear memory and stress-related behaviors in laboratory animals. Despite a well-documented line of research examining the effects of ketamine on fear memory, there is a lack of literature reviews on this important topic. Therefore, this review article summarizes the current preclinical literature on ketamine and fear memory with a particular emphasis on the route, dose, and timing of ketamine administration in rodent fear conditioning studies. Additionally, this review describes the molecular mechanisms by which ketamine may impact fear memory and stress-related behaviors. Overall, findings from previous studies are inconsistent in that fear memory may be increased, decreased, or unaltered following ketamine administration in rodents. These conflicting results can be explained by factors such as the route, dose, and timing of ketamine administration; the interaction between ketamine and stress; and individual variability in the rodent response to ketamine. This review also recommends that future preclinical studies utilize a clinically relevant route of administration and account for biological sex differences to improve translation between preclinical and clinical investigations.

Comparison of LABORAS with static incapacitance testing for assessing spontaneous pain behaviour in surgically-induced murine osteoarthritis

ObjectiveEvoked responses following mechanical or thermal stimulation are typically used to assess pain behaviour in murine osteoarthritis (OA). However, there is no consensus on how best to measure spontaneous pain behaviour. MethodOA by partial meniscectomy (PMX), or sham surgery was performed in 10-week old C57BL/6 male mice. Collagen-induced arthritis (CIA) was induced in 10 week old DBA1 male mice. Spontaneous pain behaviour, either at the time of active inflammatory disease (CIA), or over the 12 weeks after induction of OA, was assessed by static incapacitance testing (measuring percentage of weight placed through each hindlimb), and Laboratory Animal Behaviour Observation Registration and Analysis System (LABORAS) (translating cage vibrations of singly house animals into specific activities). Data were analysed by repeated measures two way ANOVA with post hoc testing comparing experimental groups with either sham operated or naïve controls. ResultsBy incapacitance testing, two phases of painful behaviour were evident after PMX: a transient, post-operative phase, which resolved within one week, and a late OA pain phase starting 8 weeks post surgery and reaching statistical significance at week 12 (95% CI: sham 89.51–98.19, PMX 76.18–98.16). LABORAS, was able to detect pain behaviour in mice with CIA, but no statistically significant pain behaviour was observed in OA mice either post operatively (once analgesia had been controlled for) or at any later time points for any activity compared with the sham group. ConclusionStatic incapacitance testing is superior to LABORAS for measuring spontaneous pain behaviour in surgically induced murine OA.