MODULATION OF MESOLIMBIC DOPAMINERGIC ACTIVITY OVER THE RAT ESTROUS-CYCLE

Clinical observations have suggested that ovarian steroid hormones mod ulate the symptomatology of psychiatric disorders and this modulation is thought to be due to a protective effect of estrogen on dopaminergi c activity. To test this hypothesis, mesolimbic dopamine (DA) activity was examined in relationship to endogenous hormone levels. Using in v ivo electrochemical techniques, K+-stimulated DA release was measured in the nucleus accumbens of control, intact cycling female rats and ex perimental rats which had received bilateral 6-hydroxydopamine (6-OHDA ) lesions to the medial prefrontal cortex (PFC) to produce subcortical hyperactivity. DA release and reuptake fluctuated with changes in cir culating steroid levels in both control and lesion groups. In non-lesi oned control rats, stimulated DA release peaked during diestrus I (DI) and was attenuated during diestrus II (DII) and estrus. DA transport, as measured by a change in T-1/2 time, was significantly potentiated during proestrus. The expression of subcortical hyperactivity followin g lesions to the medial PFC appeared to be dependent on the steroid en vironment; during DII an increased responsiveness was observed while a significant decrease in K+-stimulated release was observed during DI. These cyclic changes in DA release were not associated with dramatic changes in DA transport except during proestrus when transport was sig nificantly prolonged. These data suggest that cyclic fluctuation of ov arian steroids may modulate DA activity presynaptically through an alt eration in both release and reuptake and that this modulation effectiv ely dampens the expression of subcortical hyperactivity except under s pecific hormonal conditions. (C) 1997 Elsevier Science Ireland Ltd.