Elsevier

Behavioural Brain Research

Volume 87, Issue 2, September 1997, Pages 233-238
Behavioural Brain Research

Effects of weekly or daily exposure to the elevated plus-maze in male mice

https://doi.org/10.1016/S0166-4328(97)02286-9Get rights and content

Abstract

The elevated plus-maze is an animal model where the behavioural repertoire of rodents is used to detect effects on anxiety. Repeated testing is a procedural variable where contradictory results have been reported. Some laboratories have found stable test–retest profiles, although other studies have reported reduced open arm exploration. The objective was to further discern behavioural changes in the behaviour of the mouse after either weekly or daily tests. Behaviour was videotaped and later analysed. Behavioural patterns were encoded from an ethological point of view, a nine-pattern ethogram being employed. Other parameters such as percent time on the different sections of the maze were evaluated as well. Descriptive analysis revealed a progressive decrease in percent time spent on open arms (in weekly-tested mice), percent time on central platform, open arm entries, percent open entries, unprotected stretched attention posture (uSAP) and unprotected head-dipping (uDip), together with an augmented number of closed arm returns and percent time spent on closed arms. Taken together, these findings are consistent with an enhanced anxiety level across the tests. It is worth noting that percent time on open arms, a traditional anxiety-related parameter, was not progressively decreased in daily-tested mice. Other than expected, exploratory and locomotor elements such as sniffing, rearing, closed arm entries, and total arm entries remained quite similarly elicited throughout the tests, suggesting that locomotor habituation was not developed. However, grooming, considered a displacement response, habituated across the tests. In conclusion, the findings of the present study support the hypothesis that anxiety is enhanced after test repetition, and indicate that test–retest profiles are far from stable, except for exploratory locomotor activity.

Introduction

The elevated plus-maze is an animal model where the behavioural repertoire of rodents is used to detect effects on anxiety. It derives from the work of Montgomery [16], and it was first employed by Handley and Mithani [9]as a model of anxiety. The model has proven to be bidirectionally sensitive to manipulations of anxiety. Thus, it is suitable to detect acute anxiolytic effects of several compounds such as nitrazepam, DN-2327 and imidazolam 4, 18, 22, 28or, on the other hand, anxiogenic effects of pentylenetetrazol, DMCM and FG-7142 4, 12, 13. Anxiety effects have usually been discerned through `classical' parameters such as percent open arm entries, and percent time spent on open arms 4, 5, 7, 9, 11, 12, 17, 19, 20, 21, 22. Recently, the reliability of the test has been improved by assessing rodents' behaviour from an ethological point of view 17, 19, 20, 21, 22, 23. Thus, classical as well as ethologically derived measures are now evaluated [22]. However, a major problem with this test is that numerous variables are known to influence maze results, with the result that several contradictory findings are reported in the literature 22, 23, 27.

Repeated testing is one of the procedural variables where contradictory results have been reported. Some laboratories have found stable test–retest profiles 8, 12, 19, although the majority have reported reduced open arm exploration 7, 11, 23, 24, 26. The literature is based on inter-test intervals of days and weeks. It is well known that repeated exposure to a novel environment leads to habituation of the behavioural responses [2], emerging inactivity or stationary patterns over time [10], a fact which deserves further investigation concerning the elevated plus-maze. The objective of this study was thus to discern behavioural changes in mice after either weekly or daily test repetition, from an ethological point of view 6, 22.

Section snippets

Animals

Twenty-four Swiss male albino mice (30–35 g) from the breeding colony of the Faculty of Medicine of the University of Seville were housed in groups of six at the beginning of the experiment. They were allowed to adapt to the vivarium for at least 1 week, and were randomly assigned to two groups: weekly tested (WR, n=12) and daily tested (DR, n=12). Mice were maintained under a 12-h light/dark cycle (lights on at 08:00) in a temperature-controlled room (21.0±1.0°C). Food (laboratory chow) and

Frequency, duration and latency of patterns

Regarding frequency values, two-way ANOVA revealed significant test effects for open arm entries (F[2, 44]=6.3, P<0.01), closed arm returns (F[2, 44]=3.3, P<0.05), uSAP (F[2, 44]=16.9, P<0.0001), uDip (F[2, 44]=4.4, P<0.01), and grooming (F[2, 44]=5.9, P<0.01). Post-hoc treatment indicated that open arm entries were progressively decreased in both treatments (P<0.05, test 2; P<0.01, test 3), along with uSAP (P<0.01) and uDip (P<0.05), as shown in Table 2. Frequency of closed arm returns was

Discussion

Exploratory and locomotor elements such as sniffing, rearing, closed arm entry, and total arm entries remained quite similarly elicited across the tests. The lack of changes in these elements, mainly in closed arm entry which is considered the best measure of locomotor activity in the elevated plus-maze 4, 23, clearly indicates that locomotor habituation was not developed. Besides, immobility was little enhanced across the tests. Hence, contrary to what was expected, repeated exposure to the

Acknowledgements

This research was supported by a grant from Consejerı́a de Educación y Ciencia, Junta de Andalucı́a, Spain (research group #CVI 0127, P.A.I).

References (28)

  • Blanchard, R.J. and Blanchard, D.C., Attack and defense in rodents as ethoexperimental models for the study of emotion....
  • Claus, H.J. and Bindra, D., Reactions to novelty and stimulus-change induced response decrement, Can. J. Psychol., 14...
  • Colgan, P.W., Quantitative Ethology, 1978, Wiley, New...
  • Cruz, A.P., Frei, F. and Graeff, F.G., Ethopharmacological analysis of rat behaviour on the elevated plus-maze,...
  • Dawson G.R., Crawford, S.P., Stanhope, K.J., Iversen, S.D. and Tricklebank, M.D., One-trial tolerance to the effects of...
  • Espejo, E.F., Structure of the mouse behaviour on the elevated plus-maze test of anxiety, Behav. Brain Res., (1997) in...
  • File, S.E., One-trial tolerance to anxiolytic actions of chlordiazepoxide in the plus-maze, Psychopharmacology, 100...
  • File, S.E., Behavioral detection of anxiolytic action. In J.M. Elliott, D.J. Heal and C.A. Marsden (Eds.) Experimental...
  • Handley, S.L. and Mithani, S., Effects of alpha-adrenoceptor agonists and antagonists in a maze-exploration model of...
  • Kaesermann, H.P., Stretched attended posture, a non-social form of ambivalence, is sensitive to a conflict-reducing...
  • Lee, C. and Rodgers, R.J., Antinociceptive effects of elevated plus-maze exposure: influence of opiate receptor...
  • Lister, R.G., The use of a plus-maze to measure anxiety in the mouse, Psychopharmacology, 92 (1987)...
  • Lister, R.G., Interactions of three benzodiazepine receptor inverse agonists with ethanol in a plus-maze test of...
  • Miczek, K.A., Weerts, E.M., Vivian, J.A. and Barros, H.M., Aggression, anxiety and vocalizations in animals: GABAA and...
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