Differential effects of chlorodiazepoxide on aggressive behavior in male mice: the influence of social factors.

The present study examined the influence of prior social experience on the effects of chlordiazepoxide (CDP; 5.0, 10.0 and 20.0 mg/kg) on intrasexual aggression in male mice. Prior to drug testing, animals were either individually housed or screened in dyadic encounters in a neutral cage. This novel method yielded four experimental groups comprising animals with different social experiences and different aggressive/defensive characteristics: 1) individually-housed males (I): 2) aggressive males (A); 3) counter-attacking males (C), which actively responded to but did not initiate attack; and 4) defeated males (D). Twenty-four hours after screening, animals were treated with CDP and subjected to a resident-intruder test with untreated intruders. Results indicated that the lowest dose of CDP (5 mg/kg) increased aggressive behaviour but only in A males. At higher doses (10-20 mg/kg), CDP reduced attacks towards intruders in A, C and I, but not D, males. In A and C males, the antiaggressive action of CDP was associated with a prosocial effect (increased social investigation), whereas in I males, reduced aggression was associated with an increase in fear-related behaviours. As these differential effects of CDP on intermale aggression cannot be fully explained by differences in behavioural baselines, present data highlight the importance of experiential background as a powerful variable in determining behavioural responses to benzodiazepines. Present findings therefore suggest that an understanding of drug effects on social behaviour demands consideration of biological variability in phenotype.