Opposite genotype-dependent mesocorticolimbic dopamine response to stress

Identification of relevant phenotypes related to neural functioning has vet to receive the needed attention, although behavioral phenotyping, through comparative studies in inbred strains of mice, has produced some major find ings (Cabib et al,, 2000; Crabbe, 1999; Gerlai, 1996; Lathe, 1996). Central responses to stress play a major psychopathogenic role in the prese nce of a genetic liability (Fowels, 1992), and mesocortical and mesoacumben s dopamine metabolism and release are the most relevant among these respons es (Abercrombie et al,, 1989; Cabib and Puglisi-Allegra, 1994; Chrapusta et al,, 1997; Di Chiara et al,, 1999; Herve et al,, 1979; Imperato et al,, 19 91), Therefore, in the present study, we assessed strain-dependent differen ces in mesocortical and mesoaccumbens dopamine responses to a widely utiliz ed stressful procedure (restraint), by comparing mice of the oldest and mos t studied inbred strains (Cabib et al,, 2000): the C57BL/6JIco and DBA/2JIc o. We found that stress produced inhibition of mesoaccumbens dopamine relea se accompanied by a very fast and strong activation of mesocortical dopamin e metabolism in C57BL/6JIco mice, and the opposite in mice of the DBA12JIco strain. These results suggest a genetic control over the balance between mesocortic al and mesoaccumbens dopamine responses to stress, and provide a model for pre-clinical studies on molecular genetics of depression. (C) 2001 IBRO. Pu blished by Elsevier Science Ltd, All rights reserved.