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 probes to test both differences or similarities in neurochemical substrates (proximal causations) and adaptive significance (ultimate causations) of different forms of intraspecific aggression in wild mice and laboratory Swiss CD-1 counterparts. Fluprazine (1-5 mg/kg) inhibited maternal attack on female, but not on male intruders. Thus, phenotypically different attack behaviors (offence and defence respectively) which have different functions may be modulated by different neurochemical substrates. Intrasexual attack and infanticide which are phenotypically different, but share similar functions (i.e. competition for mates and resources) were equally inhibited by Fluprazine (2 mg/kg) both in males and females of wild and laboratory mice. This indicates that the neural substrates of these behaviors are related and similarly regulated in the two sexes. Fluprazine was used to test the prediction of the evolutionary model on fighting strategies in male-male asymmetric contests as far as fighting ability and resource value (mating and cohabitation with a female) are concerned. Fluprazine inhibited the intensity of fighting (i.e. more 'defensive' behavioral phenotype of attack) only in animals without previous positive fighting experience, suggesting that different behavioral strategies are based on different neurochemical modulation. Experience of attack also influenced the effects of CDP (2.5-5 mg/kg) in both lactating females and male resident mice. The reported proaggressive effects of benzodiazepines were observed only in animals with prior fighting experience in both cases. Thus the understanding of the effects of drugs on behavior demands consideration of the biological variability (e.g. genetic, previous experience and/or interindividual differences) and the adaptive significance of behavior in the experimental context. On this background ethopharmacology can be defined as an evolutionary approach to the study of a drugs effect on neurochemical mechanisms and functions of behavior.