Decreased accumbens dopamine release after cocaine challenge in behaviorally sensitized female rats

The effects of the competitive NMDA receptor antagonist CPP on the initiation of behavioral sensitization to acute cocaine and basal and acute cocaine-induced dopamine (DA) release in the nucleus accumbens (NAC) were assessed in female Sprague-Dawley rats. Cocaine pretreated rats (30 mg/kg IP, once daily for 7 days) challenged with cocaine (10 mg/kg) on day 8 displayed increased motor activity relative to controls challenged with cocaine on day 8. This effect was blocked in rats receiving CPP (2 mg/kg) 15 min prior to all cocaine pretreatments. Basal DA levels in the NAC of both cocaine-pretreated and CPP plus cocaine-pretreated rats were higher on day 8 compared to controls. Acute cocaine challenge on day 8 resulted in increased extracellular DA concentrations in the NAC in control rats, no increase in rats pretreated with CPP plus cocaine, and a decrease in rats pretreated with cocaine only. These data demonstrate that development of behavioral sensitization to cocaine in female Sprague-Dawley rats can be completely blocked by a peripherally administered competitive NMDA receptor antagonist and that an increase in DA release in the NAC after a cocaine challenge is not an absolute requirement for expression of motor sensitization to cocaine in female rats.