U-69593 PREVENTS COCAINE SENSITIZATION BY NORMALIZING BASAL ACCUMBENSDOPAMINE

REPEATED intermittent administration of cocaine (20 mg kg(-1), i.p.) f or 3 days dramatically increased basal dopamine (DA) overflow in the n ucleus accumbens (ACB) 48 h after the final daily injection. This coca ine pretreatment also produced a significant increase in stereotypy in response to a subsequent cocaine challenge. However, when the selecti ve kappa-opioid receptor agonist U-69593 was administered in combinati on with cocaine for 3 days, these cocaine-induced biochemical and beha vioral effects were abolished. It is suggested that the responsiveness of mesolimbic DA neurons to cocaine is intimately related to basal DA concentrations within the ACB and that U-69593, by normalizing cocain e-induced increases in basal DA overflow, may prevent the development of behavioral sensitization to cocaine.