Effects of repeated testing in two inbred strains on fiesinoxan dose-response curves in three mouse models for anxiety

Over the last decade, many genetically modified mice have been developed as models for psychiatric diseases such as anxiety. Limited availability of such mutant mice highlights the importance of studying the possibility of repeatedly testing the same individuals. We tested mice four times with 1-week intervals with the same dose of the 5-HT1A receptor agonist flesinoxan (0-0.3-1.0-3.0 mg/kg s.c.) in three anxiety-related paradigms: light-dark exploration, open-field activity and stress-induced hyperthermia. The two inbred strains studied were the highly anxious 129S6/SvEvTac (S6) and low-anxiety C57BL/6J (136) mice. The results indicate that the effects of repeated testing were relatively mild. 136 mice showed some mild habituation in the open-field test when treated with vehicle, whereas S6 mice developed reduced initial activity in the light-dark box after drug treatment. In contrast, responses to flesinoxan treatment were strong and highly consistent for most parameters. In the open-field and light-dark tests, 136 mice showed reduced activity and anxiogenic-like behavioral responses, whereas S6 mice were minimally affected. Anxiolytic-like responses were found in both strains in the stress-induced hyperthermia paradigm. We conclude that 136 and S6 mice can be tested repeatedly with agents such as 5-HT1A receptor agonists with 1-week intervals in the three paradigms tested. (C) 2004 Elsevier B.V. All rights reserved.