Repeated injections of sulpiride into the medial prefrontal cortex induces sensitization to cocaine in rats

Rationale: Recent studies have suggested that the medial prefrontal cortex (mPFC) plays an important role in the development of sensitization to cocaine. In particular, a recent report proposed that sensitization is associated with a decreased dopamine D-2 receptor function in the mPFC. The present study was designed to further examine the involvement of mPFC dopamine D-2 receptors in cocaine sensitization. Objectives: The experiments described below sought to determine the effects of acute or repeated intra-mPFC injections of the dopamine D-2 antagonist sulpiride on subsequent motor-stimulant and nucleus accumbens dopamine responses to cocaine. Methods: Rats received bilateral cannulae implants above the ventral mPFC for microinjections and above the nucleus accumbens for in vivo microdialysis. Initial studies examined the effects of intra-mPFC sulpiride pretreatment on the acute motor-stimulant and nucleus accumbens dopamine responses to cocaine. Follow-up studies determined the effects of repeated intra-mPFC sulpiride injections on subsequent behavioral and nucleus accumbens dopamine responses to a cocaine challenge. Results: Intra-mPFC sulpiride enhanced the cocaine-induced increases in motor activity and dopamine overflow in the nucleus accumbens. Repeated intra-mPFC sulpiride induced behavioral and neurochemical cross-sensitization to cocaine. Conclusions: The data support previous findings that sensitization is associated with a decrease in dopamine D-2 receptor function in the mPFC.