Discriminative stimulus effects of cocaine: Antagonism by dopamine D₁ receptor blockade in the amygdala

Mesolimbic dopamine (DA) D₁ and D₂ receptors appear to be involved in mediating the discriminative stimulus effects of cocaine. The purpose of the present study was to investigate the role of the amygdala and, in particular, central amygdala DA D₁ receptors, in modulating the stimulus effects of cocaine. Thus, rats were trained to discriminate cocaine (10 mg/kg, IP) from saline using a two-lever, water-reinforced FR 20 drug discrimination task. In substitution tests, systemic (IP) administration of cocaine (0.625-20 mg/kg) produced a dose-related increase in cocaine-lever responding. Intracranial bilateral injections of cocaine (20-200 μg, total dose) into the central amygdala engendered, at best, a partial substitution (<60% drug-lever responding) for the systemic cocaine cue. Central amygdala microinjections of artificial cerebrospinal fluid (ACSF; 1 μl/side) or SCH 23390 (0.5-2 μg, total dose) resulted in primarily saline-appropriate responding. In antagonism tests, bilateral injections of the DA D₁ receptor antagonist SCH 23390 (0.5-2 μg, total dose) into the central amygdala produced a dose-related blockade of a systemic dose of cocaine (5 mg/kg) that engendered > 85% cocaine-lever responding when given alone. Additionally, bilateral injection of a fixed dose of SCH 23390 (2 μg) into the central amygdala resulted in a rightward shift in the cocaine dose-response curve (2.5-20 mg/kg). Although administration of cocaine into the central amygdala does not mimic the systemic cocaine cue, the present results demonstrate that DA D₁ receptors located within the central amygdala appear to have a modulatory role upon the discriminative stimulus properties of cocaine.