DISCRIMINATIVE STIMULUS PROPERTIES OF COCAINE - MODULATION BY DOPAMINE D-1 RECEPTORS IN THE NUCLEUS-ACCUMBENS

Dopamine (DA) D-1 and D-2 receptors are involved in mediating the beha vioral effects of cocaine, including its discriminative stimulus prope rties. The purpose of the present study was to investigate the role of the nucleus accumbens and, in particular accum bens DA D-1 receptors in modulating the stimulus effects of cocaine. Thus, rats were trained to discriminate cocaine (10 mg/kg, IF) from saline using a two-lever, water-reinforced FR 20 drug discrimination task. In substitution test s, systemic (IF) administration of cocaine (0.625-20 mg/kg) produced a dose-related increase in cocaine-appropriate responding. Microinjecti ons of cocaine (2.5-40 mu g) into the nucleus accumbens also engendere d dose-dependent and complete substitutions (>80% drug-lever respondin g) for the systemic training dose of cocaine, whereas intra-accumbens artificial cerebrospinal fluid (1 mu l/side) produced primarily saline -appropriate responding. In antagonism tests, pretreatment with the DA D-1 antagonist SCH 23390 (3-12 mu g/kg) completely antagonized (<20% drug-lever responding) a dose of cocaine (5 mg/kg) that produced great er than 90% cocaine-lever responding when given alone. Additionally, i ntra-accumbens injections of SCH 23390 (0.025-0.4 mu g) prior to syste mic cocaine (5 mg/kg) also significantly blocked the cocaine stimulus. The present results confirm the importance of the nucleus accumbens i n mediating the discriminative stimulus properties of cocaine and sugg est a primary role of accumbens DA D-1 receptors in modulating this be havior.