Dopamine depletion in the medial prefrontal cortex induces sensitized-likebehavioral and neurochemical responses to cocaine

It has been postulated that behavioral sensitization to cocaine is associat ed with an attenuation of cocaine-induced dopamine (DA) transmission in the medial prefrontal cortex (mPFC). Hence, experiments were designed to exami ne the effects of chemically-induced cortical DA depletion on the acute beh avioral and neurochemical responses to cocaine. One week following two bila teral 6-hydroxydopamine (6-OHDA) injections into the mPFC, animals received injections of cocaine (7.5, 15 or 30 mg/kg, i.p.) or saline (1 ml/kg, i.p. ) in a randomized fashion with a minimum 3 day intertrial interval. Cocaine produced a dose-dependent increase in motor activity which was significant ly enhanced in animals depleted (mean of 76%) of dopamine in the mPFC. Like wise, 6-OHDA lesions of the mPFC produced a significant enhancement of coca ine-induced DA transmission in the nucleus accumbens (NAC) as estimated by in vivo microdialysis. These data indicate a permissive involvement of cort ical DA in mediating behavioral and neurochemical responses to cocaine, as well as confirm the ability of the mPFC to influence subcortical structures in response to an acute injection of cocaine. Collectively, the present fi ndings suggest that alterations in cortical DA transmission may be a neural substrate mediating the development of sensitization to cocaine, and thus, may contribute to the addictive properties of cocaine. (C) 1999 Elsevier S cience B.V. All rights reserved.