Role of genotype in the adaptation of the brain dopamine system to stress

Behavioral and biochemical analysis of the effects of stress on brain dopamine (DA) functioning in two inbred strains of mice reveals opposite patterns of adaptation to chronic stress. Chronically stressed mice of the C57BL/6 (C57) strain are characterized by hypersensitive mesolimbic DA autoreceptors and by a dramatic increase of D1/D2 DA receptor ratio (possibly postsynaptic) in the nucleus accumbens septi (NAS) as revealed by in vivo binding of 3 H-spiperone and 3 H-SCH23390. Chronically stressed DBA/2 (DBA) mice present, on the contrary, hyposensitive DA autoreceptors and no changes in the D1/D2 DA receptors ratio in this brain area. The analysis of the behavioral responses of chronically stressed mice of the C57 strain to the mixed D1/D2 receptor agonist apomorphine, to the selective D2 agonist LY171555 and to the selective D1 agonist SKF 38393 suggest a close relationship between the behavioral alterations produced by chronic stress and the alterations of sensitivity of D2 pre- and postsynaptic receptors in the mesolimbic system. Furthermore, chronically stressed C57 mice present a marked decrease of spontaneous-climbing behavior which is not observed in the mice of the DBA strain and is dependent on the alteration of the biphasic evolution of this behavior during exposure to the test situation which, for these mice, represents a novel environment. Acute exposure to aversive environmental conditions induces a biphasic alteration of DA transmission (initial increase of DA release followed by a decrease under control levels) in the NAS. In light of these results, it is postulated that chronic stress exposure reduces or eliminates in C57 mice a behavioral strategy adopted during exposure to aversive situations possibly due to altered DA receptor sensitivity in the mesolimbic system. The alterations of DA functioning observed in DBA mice following chronic stress might represent, on the contrary, compensatory mechanisms leading to the maintenance of this response.