Pharmacological Investigation of Serial Anxiety Tests in the Mouse: A Pilot Study (original) (raw)
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Measuring anxiety- and locomotion-related behaviours in mice: a new way of using old tests
Psychopharmacology, 2010
Rationale Batteries of tests that are thought to measure different aspects of anxiety-related behaviour are used to characterise mice after genetic or pharmacological manipulation. However, because of the potentially confounding effects of repeated testing and natural intra-individual variations in behaviour over time, subjecting mice to a succession of tests is not ideal.
The use of the elevated plus maze as an assay of anxiety-related behavior in rodents
Nature protocols, 2007
The elevated plus maze is a widely used behavioral assay for rodents and it has been validated to assess the anti-anxiety effects of pharmacological agents and steroid hormones, and to define brain regions and mechanisms underlying anxiety-related behavior. Briefly, rats or mice are placed at the junction of the four arms of the maze, facing an open arm, and entries/duration in each arm are recorded by a video-tracking system and observer simultaneously for 5 min. Other ethological parameters (i.e., rears, head dips and stretched-attend postures) can also be observed. An increase in open arm activity (duration and/or entries) reflects anti-anxiety behavior. In our laboratory, rats or mice are exposed to the plus maze on one occasion; thus, results can be obtained in 5 min per rodent.
Physiology & Behavior, 1997
AVGUSTINOVICH, D. F., O. V. GORBACH AND N. N. KUDRYAVTSEVA. Comparative analysis of anxiety-like behavior in partition and plus-maze tests after agonistic interactions in mice. PHYSIOL BEHAV 61( 1 ) 37-43, 1997.--The behavior of C57BL/6J male mice with experience of repeated victories (winners) or defeats (losers) in daily agonistic interactions, was examined in the plus-maze and partition tests. The latter procedure assesses the reactivity of mice to another conspecific in the neighboring compartment of a common cage, communicative behavior or level of sociability. The behavior of mice after 10 days (T 10) and 20 days (T20) of agonistic confrontations, as well as in controls (5 days of individual housing) was analyzed. Significant differences were found between T10 and T20 losers and controls in both tests. In the partition test, a decrease in the number of approaches and total and average time spent near the partition was found in T10 and, more pronounced, in T20 losers. In the plusmaze, losers showed fewer open and total entries than controls. Moreover, rarely did they pass from one enclosed arm to another, and also showed a decreased number of 'peepings' from enclosed arms. Percentage of open time did not differ significantly in losers compared to controls. It is suggested that the level of losers' sociability, estimated as low by the partition test, can include anxiety as a component, which is confirmed, at least partly, by some parameters of the plus-maze test. There were no differences in the partition or plus-maze tests between T10 winners and controls. However, all parameters of partition behavior were significantly different between T20 winners and controls. In the plus-maze, similar to losers, T20 winners displayed fewer open ann entries, number of 'peepi,'ags,' and passages than controls. It was concluded that parameters of the partition and plus-maze tests correlate in mice with the alternative experience of agonistic confrontations, positive or negative. A combination of these two tests may be used for estimation of developing anxiety in mice.
Measuring normal and pathological anxiety-like behaviour in mice: a review
Behavioural Brain Research, 2001
Measuring anxiety-like behaviour in mice has been mostly undertaken using a few classical animal models of anxiety such as the elevated plus-maze, the light/dark choice or the open-field tests. All these procedures are based upon the exposure of subjects to unfamiliar aversive places. Anxiety can also be elicited by a range of threats such as predator exposure. Furthermore, the concepts
Validation of open : closed arm entries in an elevated plus-maze as a measure of anxiety in the rat
Journal of Neuroscience Methods, 1985
A novel test for the selective identification of anxiolytic and anxiogenic drug effects in the rat is described, using an elevated 4--maze consisting of two open arms and two enclosed arms. The use of this test for detecting such drug effects was validated behaviourally, physiologically, and pharmacologically. Rats made significantly fewer entries into the open arms than into the closed arms, and spent significantly less time in open arms. Confinement to the open arms was associated with the observation of significantly more anxiety-related behaviours, and of significantly greater plasma corticosterone concentrations, than confinement to the closed arms. Neither novelty nor illumination was a significant contributor to the behaviour of the rats on the +-maze. A significant increase in the percentage of time spent on the open arms and the number of entries into the open arms was observed only within clinically effective anxiolytics (chlordiazepoxide, diazepam and, less effectively, phenobarbitone). Compounds that cause anxiety in man significantly reduced the percentage of entries into, and time spent on, the open arms (yohimbine, pentylenetetrazole, caffeine, amphetamine). Neither antidepressants nor major tranquilisers had a specific effect. Exposure to a holeboard immediately before placement on the +-maze showed that behaviour on the maze was not clearly correlated either with exploratory head-dipping or spontaneous locomotor activity.
Comparisons between anxiety tests for selection of anxious and non anxious mice
Behavioural Brain Research, 2006
Male Swiss albinos mice were submitted to two behavioural tests intended to determine their anxiety level: the elevated plus-maze test as well as the black and white compartments test. In addition they were submitted to the hole-board test. It was observed: (i) that the correlation between scores in the two first tests was weak, suggesting that they explore different components of anxiety; (ii) that the score on the latter test was better correlated with the response in the elevated plus-maze test than in the black and white compartments test. From these data three groups of animals were constituted, considered, respectively, as anxious, non anxious and intermediates. It was observed that both horizontal and vertical locomotion in an unfamiliar environment differed between groups, with higher activity in non anxious than in anxious. In the hole-board test, only animals classified as anxious displayed an obvious response to the anxiolytic drug diazepam (0.5 mg/kg). Finally in the forced-swimming test, the three groups demonstrated a similar immobility time, suggesting that the operated segregation was not depending on a helpless component. It is proposed that the selection of mice from a combination of either elevated plus-maze and black and white compartments tests or a combination of hole-board test and black and white compartments test, allows to distinguish high or low anxiety animals among a population of mice.
Pharmacology Biochemistry and Behavior, 2015
The free-exploratory paradigm (FEP) has been proposed as a model of trait anxiety for both mice and rats. However, its pharmacological validation has only been carried out for mice. Thus, the aim of the present study was to pharmacologically validate FEP for Wistar rats, by testing the effects of clinically established anxiolytic and anxiogenic drugs, in four different experiments. In all experiments, male Wistar rats were first tested in FEP to be categorized according to their levels of trait anxiety (high, medium and low). Then, only medium trait anxiety rats were selected to be tested again in FEP, two weeks later, after being pharmacologically treated, according to each experiment as follows: Experiment I: 0.5 mg/kg of diazepam (DZP) or vehicle; Experiment II: 20 mg/kg of pentylenetetrazole (PTZ) or vehicle; Experiment III: 5 mg/kg of fluoxetine (FLX5) or vehicle: and Experiment IV: 0.5 mg/kg of fluoxetine (FLX0.5) or vehicle. As a group, the results showed that PTZ and FLX5 increased levels of trait anxiety and reduced locomotor activity, whereas DZP and FLX0.5 decreased levels of trait anxiety, without impairing locomotor activity. These results demonstrate that FEP for rats is able to predict clinical anxiolytic and anxiogenic activities of different drugs, including fluoxetine, which is believed to present a dual effect on anxiety. Therefore, this paradigm can be proposed as an effective method for testing potential trait anxiety-reducing drugs, in rats.
Physiology & Behavior, 2017
Ample studies ha ve shown that housing can affect the health, welfare and behavior of mice and therefore, the outcomes of certain experiments. The aim of this study was to investigate if three widely used housing systems, Open Top Cages (OTC), Motor Free Ventilated Cages (MFVC) and Individually Ventilated Cages (IVC) may affect exploratory and anxiety-related behaviors in mice. Subjects were 8 week-old male C57Bl/6J mice (n=36) divided into three groups, OTC, IVC and MFVC groups, respectively. The experimental procedure consisted of two behavioral tests: the open field and the elevated plus maze test. Although there were no differences in the open field test, the results from the elevated plus maze showed that animals housed in the MFVCs exhibited increased exploratory and less anxiety-like behavior. It is concluded that the different caging systems may have an impact on the outcome of behavioral tests used to assess exploratory and anxiety like behavior in mice. Therefore, it is essential to housing conditions into consideration when reporting, analyzing, and/or systematically reviewing the results of behavioral testing in mice.
Animal models of anxiety in mice
Fundamental & Clinical Pharmacology, 2007
Among the multiple possibilities to study human pathologies, animal models remain one of the most used pathways. They allow to access to unavailable answers in human patients and to learn about mechanisms of action of drugs. Primarily developed with rats, animal models in anxiety have been adapted with a mixed success for mice, an easy-to-use mammal with better genetic possibilities than rats. In this review, we have focused on the most used animal models in anxiety in mice. Both conditioned and unconditioned models are described, to represent all types of animal models of anxiety. Behavioural studies require strong care for variable parameters, linked to environment, handling or paradigm; we have discussed about this topic. Finally, we focused on the consequences of re-exposure to the apparatus. Test-retest procedures can bring in new answers, but should be deeply studied, to revalidate the whole paradigm as an animal model of anxiety.