The role of prefrontal cortex D1-like and D2-like receptors in cocaine-seeking behavior in rats

Rationale: Evidence from preclinical and clinical studies indicates an important role for the mesocorticolimbic dopamine system in cocaine craving and relapse. Objectives: To investigate the relative involvement of prefrontal cortex D1-like and D2-like dopamine receptors in cocaine-primed, drug-seeking behavior. Methods: Rats were trained to press a lever to self-administer cocaine (i.v., 0.25 mg per infusion) in daily 2-h sessions. Responding was reinforced, contingent on a modified fixed-ratio 5 schedule. Reinstatement tests began after lever-pressing behavior was extinguished in the absence of cocaine and conditioned cues ( light and tone). Before each reinstatement test, rats received bilateral microinfusions of different doses of selective D1-like and D2-like antagonists, SCH 23390, and eticlopride, respectively, followed by intraperitoneal administration of 10 mg/kg cocaine; 3 min later the session started. Responding in the reinstatement test was reinforced only by the conditioned cues contingent on a fixed-ratio 5 schedule. Results: Both drugs dose dependently decreased cocaine-primed reinstatement without affecting operant behavior maintained by food. Eticlopride, but not SCH 23390, increased cocaine self-administration and decreased food-primed reinstatement at the dose found to decrease cocaine-primed reinstatement. Conclusions: These data suggest that, although both D1-like and D2-like receptors in the prefrontal cortex are involved in cocaine-primed drug-seeking behavior, they may modulate different aspects of this process.