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 neurotransmi tter activity represent a major strategy in the investigation of the n eurochemical bases underlying behavioral expression. Moreover, these s tudies represent a preliminary stage in behavioral genetic research si nce they allow quantitative scales to be established and suggest corre lations to be tested in recombinant inbred strains. The present review evaluates results obtained in mice of the C57BL/6 (C57) and DBA/2 (DB A) inbred strains which have been used for studies of the behavioral p harmacology of dopamine (DA) and investigated for the functional and a natomical characteristics of their brain DA systems. Differences betwe en C57 and DBA strain involve susceptibility and sensitivity as well a s 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 pr ovide important indications about the relationship between behavioral and central effects of DA agonists and, more generally, about the invo lvement of brain DA in behavior. Comparative studies in C57 and DBA mi ce have also revealed differences in susceptibility to context-depende nt, 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 di fferent, independent genotype-related factors play a major role. Final ly, studies on the behavioral and central effects of stressful experie nces in C57 and DBA mice together with psychopharmacogenetic analyses, indicate that different symptomatological profiles may derive from ge notype-dependent adaptation of brain DA receptors to environmental pre ssure. (C) 1997 Elsevier Science Ltd.