Estrogen effects on cocaine-induced reinstatement of lever responding were examined in sham-operated, vehicle-treated (SH+VEH), ovariectomized (OVX+VEH), and OVX female Wistar rats with estrogen replacement (OVX+EB). The effect of long- (64+/-1.56 days) and short-term (9 days) EB treatment on reinstatement of cocaine-seeking behavior was compared in Experiment 1 and 2, respectively, in order to compare the effect of EB when it was present during the development vs. expression of reinstatement of cocaine-seeking behavior. Rats were trained to self-administer 0.4 mg/kg/inf cocaine. After the acquisition criteria were met, rats continued to respond for cocaine for 2 h/day for a 14-day maintenance period. Cocaine was then replaced with saline and the 21-day extinction period commenced. Subsequently, rats were tested for reinstatement of lever responding on the previously drug-paired lever after alternating daily injections of saline or cocaine. In both experiments, there were no differences between groups in self-administration behavior during training, maintenance, or extinction. In Experiment 1, SH+VEH and chronically treated OVX+EB rats had greater cocaine-induced reinstatement than OVX+VEH rats. In Experiment 2, short-term treated OVX+EB rats also showed enhanced cocaine-induced reinstatement compared to OVX+VEH rats. The results indicate that EB-mediated enhancement of cocaine-induced reinstatement is dependent on EB presence during the expression of reinstatement but not during the formation of stimulus-reward associations during the development of cocaine-reinforced behavior.
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