Prior test experience compromises the anxiolytic efficacy of chlordiazepoxide in the mouse light/dark exploration test

It is now well established that prior test experience can alter behavioural baselines and attenuate/abolish the anxiolytic efficacy of benzodiazepines in the elevated plus-maze paradigm. In View of evidence that different mod els of anxiety measure qualitatively distinct forms of anxiety-like behavio ur, it is important to establish whether the effects of prior experience ex tend to other widely-used tests. The present study assessed the behavioural and pharmacological sequelae of a single undrugged prior exposure to the l ight/dark exploration (L/D) test in mice, using ethological scoring methods . One group of adult male Swiss-Webster mice was given a single undrugged e xposure to the L/D test 24 h prior to drug testing, while another group was completely naive to the apparatus. On test day, half the animals in each e xperiential condition were treated with saline and half with an anxiolytic dose (10 mg/kg) of chlordiazepoxide (CDP). When administered to test-naive animals, CDP induced a clear reduction in anxiety-like behaviour as evidenc ed by significant increases in exploration of the light compartment (line c rossings, % line crossings, and % time) as well as reductions in stretched attend postures (SAPs) and the proportion of SAPs displayed toward the ligh t compartment. The behavioural specificity of these effects was confirmed b y the absence of a drug effect on line crossings in the dark compartment, t otal rearing and grooming. In complete contrast, with the sole exception of a decrease in total SAPs, CDP was without significant behavioural effect i n test-experienced mice. As prior test experience did not significantly alt er behavioural baselines in the L/D test, a second experiment was designed to investigate the possibility that handling/intraperitoneal injection may have precluded detection of experientially-induced changes in baseline beha viour. Results showed that handling/injection had no effect upon L/D behavi oural profiles in either test-naive or test-experienced subjects, and confi rmed that prior experience itself did not modify the primary indices of anx iety in this test. Present data indicate that prior test experience serious ly compromises the anxiolytic efficacy of CDP (10 mg/kg) in the mouse L/D t est and, together with recent findings in the four-plate test, appear to co nfirm that an experientially-induced reduction in sensitivity to the anxiol ytic effects of benzodiazepines is by no means unique to the elevated plus- maze. (C) 2001 Elsevier Science B.V. All rights reserved.