Characterization of the Role of Medial Prefrontal Cortex Dopamine Receptors in Cocaine-Induced Locomotor Activity

Medial prefrontal cortex (mPFC) dopamine (DA) modulates the motor-stimulant response to cocaine. The present study examined the specific mPFC DA receptor subtypes that mediate this behavioral response. Intra-mPFC injection of the DA D 2 -like receptor agonist quinpirole blocked cocaine-induced motor activity, an effect that was prevented by coadministration of the D 2 receptor antagonist sulpiride. Intra-mPFC injection of the selective D 4 receptor agonist PD 168,077 or the selective D 1 receptor agonist SKF 81297 did not alter the motor-stimulant response to cocaine. Finally, it was found that an intermediate dose of quinpirole, which only attenuated cocaine-induced motor activity, was not altered by SKF 81297 coadministration, suggesting a lack of synergy between mPFC D 1 and D 2 receptors. These results suggest that D 2 receptor mechanisms in the mPFC are at least partly responsible for mediating the acute motor-stimulant effects of cocaine.