OPPOSITE EFFECTS OF STRESS ON DOPAMINE RELEASE IN THE LIMBIC SYSTEM OF DRUG-NAIVE AND CHRONICALLY AMPHETAMINE-TREATED RATS

The effects of repeated amphetamine administration on stress-induced d opamine release in the ventral striatum were examined in male Wistar r ats treated with D-amphetamine (1.5 mg/kg; i.p./injection) or saline a t 12 h intervals for 14 days. After 12 h as well as 7 days of amphetam ine withdrawal, dopamine release was monitored by transverse microdial ysis under basal conditions and during exposure to 60 min of restraint stress. Basal dopamine release was significantly suppressed relative to saline-pretreated controls after both 12 h and 7 days of amphetamin e withdrawal. In control rats, restraint stress resulted in significan tly increased dopamine efflux. In contrast. exposure to this stressor was associated with a significant suppression of dopamine release in r ats chronically exposed to amphetamine. This effect was observed at bo th post-amphetamine test points. The results suggest that chronic amph etamine impairs the dopaminergic response to stress and that this dopa minergic deficit may play a role in stress-induced drug-seeking behavi or and relapse. (C) 1997 Elsevier Science B.V.