Intra-medial prefrontal cortex injection of quinpirole, but not SKF 38393,blocks the acute motor-stimulant response to cocaine in the rat

Rationale: Considerable evidence suggests that the medial prefrontal cortex (mPFC) is an important region in mediating certain behavioral and neuroche mical responses to cocaine. However, a role for cortical dopamine (DA) rece ptor subtypes in modulating these responses has yet to be elucidated. Objec tives: This study investigated the effects of intra-mPFC administration of DA agonists on the acute motor-stimulant response to cocaine. In addition, in vivo microdialysis techniques were employed to determine the effects of intracortical injection on cocaine-induced extracellular DA concentrations in the nucleus accumbens (NAC). Methods: One week following bilateral cannu lae implantation over the mPFC and the NAC (for dialysis experiments), male Sprague-Dawley rats received an intra-mPFC injection of saline, the DA D2- like agonist quinpirole (0.015, 0.05, 0.15, 0.5, 1.5, or 5.0 nmol per side) or the partial DA D1-like agonist SKF 38393 (0.5, 1.5, or 5.0 nmol per sid e) approximately 5 min before peripheral administration of saline or cocain e (15 mg/kg, i.p.). For dialysis experiments, only the highest dose of quin pirole was examined. Results: Pretreatment with quinpirole produced a dose- dependent decrease in cocaine-induced motor activity, with the highest dose s resulting in a complete abolition of the acute motor-stimulant response t o cocaine. In contrast, intra-mPFC administration of SKF 38393 was not show n, at the doses tested, to alter cocaine-induced motor activity. In agreeme nt with the behavioral effects, intra-mPFC quinpirole injection (5 nmol per side) significantly blocked cocaine-induced DA overflow in the NAG. Conclu sions: The results of the present study provide additional support that the mPFC is a neural substrate through which cocaine, in part, produces its mo tor-stimulant effects. In addition, these data suggest that modulation of c ortical DA D2 receptors can block;scute cocaine-induced behavioral (locomot or activity) and neurochemical (DA concentrations in the NAC) responses in the rat.