AbstractThe behavioral stimulant effect of peripheral cocaine injection into rats is augmented following daily adminstration. In vivo dialysis in the nucleus accumbens of conscious rats was used to determine if the increased behavioral response following daily cocaine administration is associated with in increase in extracellular dopamine concentration. Acute injection of cocaine (15 mg/kg, ip) produced and elevation in extracellular dopamine concentration in the nucleus accumbens. Following daily pretreatment with cocaine (15 mg/kg, ip × 4 days), a subsequent acute injection of cocaine (15 mg/kg, ip) significantly elevated the extracellular dopamine levels compared to that produced by a single acute injection. Although the levels extracellular dopamine metabolites was significantly lowered by both acute cocaine and daily cocaine, no difference between these two groups of animals was measured. The increase in extrecellular dopamine following a single acute injection of cocaine was not correlated to the motor stimulant response. However, after daily pretreatment with cocaine the motor stimulant response to acute cacaine was positively correlated with the increased extracellular concentration of dopamine in the nucleus accumbens. These data demonstrate that enhanced dopamine release into the nucleus accumbens may mediate the behavioral sensitization produced by daily injections of cocaine, but that other neural systems are influential in mediating the acute motor stimulant effect of cocaine