Abstract
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.
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