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