Opposite genotype-dependent mesocorticolimbic dopamine response to stress

Identification of relevant phenotypes related to neural functioning has yet to receive the needed attention, although behavioral phenotyping, through comparative studies in inbred strains of mice, has produced some major findings (Cabib et al., 2000; Crabbe, 1999; Gerlai, 1996; Lathe, 1996). Central responses to stress play a major psychopathogenic role in the presence of a genetic liability (Fowels, 1992), and mesocortical and mesoacumbens dopamine metabolism and release are the most relevant among these responses (Abercrombie et al., 1989; Cabib and Puglisi-Allegra, 1994; Chrapusta et al., 1997; Di Chiara et al., 1999; Hervé et al., 1979; Imperato et al., 1991). Therefore, in the present study, we assessed strain-dependent differences in mesocortical and mesoaccumbens dopamine responses to a widely utilized stressful procedure (restraint), by comparing mice of the oldest and most studied inbred strains (Cabib et al., 2000): the C57BL/6JIco and DBA/2JIco. We found that stress produced inhibition of mesoaccumbens dopamine release accompanied by a very fast and strong activation of mesocortical dopamine metabolism in C57BL/6JIco mice, and the opposite in mice of the DBA/2JIco strain. These results suggest a genetic control over the balance between mesocortical and mesoaccumbens dopamine responses to stress, and provide a model for pre-clinical studies on molecular genetics of depression.