THE D-1 AGONIST SKF-38393 ATTENUATES AMPHETAMINE-PRODUCED ENHANCEMENTOF RESPONDING FOR CONDITIONED REWARD IN RATS

The present study investigated the hypothesis that the D-1 subtype of DA receptors is critically involved in reward-related learning. The ef fects of SKF 38393, a D-1-specific agonist, on amphetamine-produced en hancement of responding for conditioned reward were tested. We exposed 69 male Wistar rats to an experimental design consisting of three pha ses. The preexposure phase consisted of five sessions during which the rats were exposed to an operant chamber containing two levers. One le ver produced a lights-off stimulus (3 s) and the other a tone stimulus (3 s). This was followed by four conditioning sessions during which t he levers were removed and the rats were exposed to pairings of the li ghts-off stimulus with food. This phase was followed by two test sessi ons during which the levers were present and the number of responses m ade on each lever was calculated as a ratio of the number of responses made during the preexposure phase. A group receiving saline during th e test sessions showed a higher ratio of responding for the lights-off stimulus than the tone stimulus, demonstrating that the lights-off st imulus had become a conditioned reward. Amphetamine [2.0 mg/kg, intrap eritoneally (IP), 5 min before the test] enhanced responding specifica lly on the lever producing the conditioned reward. Groups receiving SK F 38393 (5.0, 10.0, and 20.0 mg/kg, IP, 5 min before the test) failed to show significantly greater responding for the lights-off stimulus t han the tone, indicating a reduction or elimination of the conditioned reward effect. Moreover, SKF 38393 dose dependently reduced the amphe tamine-produced enhancement of responding for conditioned reward. The possible role for D-1 receptors in reward-related learning is discusse d.