An evolutionary approach to behavioral pharmacology: using drugs to understand proximate and ultimate mechanisms of different forms of aggression in mice

Psychoactive drugs (Fluprazine and Chlordiazepoxide - CDP) were used as pro bes to test both differences or similarities in neurochemical substrates (p roximal causations) and adaptive significance (ultimate causations) of diff erent forms of intraspecific aggression in wild mice and laboratory Swiss C D-1 counterparts. Fluprazine (1-5 mg/kg) inhibited maternal attack on femal e, but not on male intruders. Thus, phenotypically different attack behavio rs (offence and defence respectively) which have different functions may be modulated by different neurochemical substrates. Intrasexual attack and in fanticide which are phenotypically different, but share similar functions ( i.e. competition for mates and resources) were equally inhibited by Flupraz ine (2 mg/kg) both in males and females of wild and laboratory mice. This i ndicates that the neural substrates of these behaviors are related and simi larly regulated in the two sexes. Fluprazine was used to test the predictio n of the evolutionary model on fighting strategies in male-male asymmetric contests as far as fighting ability and resource value (mating and cohabita tion with a female) are concerned. Fluprazine inhibited the intensity of fi ghting (i.e. more 'defensive' behavioral phenotype of attack) only in anima ls without previous positive fighting experience, suggesting that different behavioral strategies are based on different neurochemical modulation. Exp erience of attack also influenced the effects of CDP (2.5-5 mg/kg) in both lactating females and male resident mice. The reported proaggressive effect s of benzodiazepines were observed only in animals with prior fighting expe rience in both cases. Thus the understanding of the effects of drugs on beh avior demands consideration of the biological variability (e.g. genetic, pr evious experience and/or interindividual diferences) and the adaptive signi ficance of behavior in the experimental context. On this background ethopha rmacology can be defined as an evolutionary approach to the study of a drug s effect on neurochemical mechanisms and functions of behavior. (C) 1998 El sevier Science Ltd. All rights reserved.