Psychopharmacology of dopamine: The contribution of comparative studies in inbred strains of mice

Comparative studies of behavioral responses to centrally acting drugs in inbred strains of mice which show differences in brain neurotransmitter activity represent a major strategy in the investigation of the neurochemical bases underlying behavioral expression. Moreover, these studies represent a preliminary stage in behavioral genetic research since they allow quantitative scales to be established and suggest correlations to be tested in recombinant inbred strains. The present review evaluates results obtained in mice of the C57BL/6 (C57) and DBA/2 (DBA) inbred strains which have been used for studies of the behavioral pharmacology of dopamine (DA) and investigated for the functional and anatomical characteristics of their brain DA systems. Differences between C57 and DBA strain involve susceptibility and sensitivity as well as qualitative differences in the type or; direction of the behavioral effects of DA agonists. Moreover, data on strain-dependent differences for DA metabolism, release and receptor densities and distribution provide important indications about the relationship between behavioral and central effects of DA agonists and, more generally, about the involvement of brain DA in behavior. Comparative studies in C57 and DBA mice have also revealed differences in susceptibility to context-dependent, context-independent and stress-induced behavioral sensitization to psychostimulants. Consequently, they support the view that the term ''behavioral sensitization'' may define different phenomena in which different, independent genotype-related factors play a major role. Finally, studies on the behavioral and central effects of stressful experiences in C57 and DBA mice together with psychopharmacogenetic analyses, indicate that different symptomatological profiles may derive from genotype-dependent adaptation of brain DA receptors to environmental pressure. (C) 1997 Elsevier Science Ltd.