Dopamine D1 receptor activation in the medial prefrontal cortex prevents the expression of cocaine sensitization

This study examined whether microinjection of the full D1 agonist, SKF 8129 7, or the D1 antagonist, SCH 23390, into the medial prefrontal cortex (mPFC ) would alter the expression phase of cocaine sensitization. Male Sprague-D awley rats were administered saline or cocaine (15 mg/kg, i.p.) once per da y for seven consecutive days. After 8 to 17 days withdrawal, rats received a bilateral intra-mPFC microinjection of SKF 81297: either 0, 0.03, 0.1, or 0.3 mug/side; SCH 23390: either 0, 0.1, 0.3, or 1.0 mug/side; or a combina tion of 0.1 mg of SKF 81297 +/- 0.3 mg of SCH 23390, followed by an i.p. sa line or cocaine (15 mg/kg, i.p.) injection. In naive rats, vertical activit y was elevated by the two lower doses of SKF 81297. A similar enhancement o f cocaine-induced activity was observed in daily saline rats at the highest dose tested. In contrast, SKF 81297 suppressed the expression of sensitiza tion to cocaine. This blockade of sensitization was prevented by coinfusion of SCH 23390. Infusion of SCH 23390 alone into the mPFC in daily saline an d cocaine-pretreated rats demonstrated a suppression of cocaine-induced loc omotion in daily saline-pretreated rats after the highest dose, but a sligh t augmentation of activity after the lowest dose in daily cocaine-pretreate d rats. These results demonstrate a contribution by mPFC D1 receptors in th e expression of cocaine sensitization and further suggest that the effects of D1 receptor activation in the mPFC occur in opposite directions in daily saline versus daily cocaine-pretreated rats.