Effect of medial prefrontal cortex injections of SCH 23390 on intravenous cocaine self-administration under both a fixed and progressive ratio schedule of reinforcement.

Rats were trained to self-administer cocaine (1.5 mg/kg i.v.) under either a fixed ratio (FR) or progressive ratio (PR) schedule of reinforcement. Following acquisition, bilateral intracerebral cannulae were directed at the medial prefrontal cortex (mPFC) or striatum (STRM). Intracranial injections of the D1 receptor antagonist, SCH 23390 (0-2.0 micrograms/0.5 microliter/side), were made immediately prior to a self-administration session. Under the FR 1 schedule, SCH 23390 caused a dose-dependent increase in the rate of cocaine intake following injection into either the mPFC or the STRM. In contrast, under the PR schedule similar injections into the STRM had no effect on the breaking point, but large decreases were produced following injection into the mPFC. These results indicate that dopaminergic systems within the mPFC have a significant role to play in the reinforcing properties of cocaine. Moreover, the STRM does not appear to have a role in those reinforcing properties of cocaine measured under the PR schedule. The significant rate-increasing effects obtained from the STRM under the FR schedule, indicate that the two schedules must measure different aspects of cocaine's CNS action.