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 D₂ receptor function in the mPFC. The present study was designed to further examine the involvement of mPFC dopamine D₂ receptors in cocaine sensitization.Objectives The experiments described below sought to determine the effects of acute or repeated intra-mPFC injections of the dopamine D₂ 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 D₂ receptor function in the mPFC.