Differences in anxiety-related behaviours and in sensitivity to diazepam in inbred and outbred strains of mice

Rationale: Natural strain differences exist in mice for behavioural traits such as emotional reactivity. Objective: The present experiments compared t he behavioural profiles of nine strains of mice (BALB/c, C57BL/6, C3H, CBA, DBA/2, NMRI, NZB, SJL, Swiss) in two models of anxiety after the administr ation of the benzodiazepine diazepam. Methods: The tests used were the ligh t/dark choice task and the elevated plus-maze, two well-validated anxiolyti c screening tests. Results: In vehicle-treated animals, differences on vari ables designed to measure anxiety-related behaviours were observed in both tests. In the light/dark test, the strains could be divided into three dist inct groups: two non-reactive strains (NZB and SJL), an intermediate-reacti ve group (C3H, CBA, DBA/2, NMRI, C57BL/6 and Swiss), and one highly reactiv e strain (BALB/c). In the elevated plus-maze, SJL, NMRI, CBA and, to a less er extent, C3H strains of mice, consistently showed low levels of anxiety-r elated behaviours. Intermediate levels were seen in the Swiss and BALB/c st rains, and high levels of emotional reactivity were seen in C57BL/6, DBA/2 and NZB. The strain distribution between the light/dark and the elevated pl us-maze tests shows similarities and differences, suggesting that each of t hese experimental procedures represents a different set of behaviours. Mark ed differences between a number of strains of mice in their sensitivity to the anxiolytic-like action of diazepam were observed in both the light/dark and the elevated plus-maze tests. Mice of the BALB/c, Swiss and, to a less er extent, CBA and C3H strains were responsive to diazepam in both tests, a lthough in the case of CBA mice, effects may have been contaminated by beha vioural suppression. SJL mice were largely unresponsive to the action of th e benzodiazepine in both tests, whereas in C57, DBA/2, NMRI and NZB mice, d iazepam produced positive effects only in the elevated plus-maze. Conclusio n: The finding of differential strain distributions both with and without d iazepam treatment in the light/dark and the elevated plus-maze tests. indic ates that not all strains of mice are Suitable for investigating the effect s of GABA/BZ receptor ligands. This study may thus provide a useful guide f or choosing the best strain of mice for studying the pharmacology of fear-r elated behaviours.