The D1 agonist SKF 38393 attenuates amphetamine-produced enhancement of responding for conditioned reward in rats

The present study investigated the hypothesis that the D1 subtype of DA receptors is critically involved in reward-related learning. The effects of SKF 38393, a D1-specific agonist, on amphetamine-produced enhancement of responding for conditioned reward were tested. We exposed 69 male Wistar rats to an experimental design consisting of three phases. The preexposure phase consisted of five sessions during which the rats were exposed to an operant chamber containing two levers. One lever produced a lights-off stimulus (3 s) and the other a tone stimulus (3 s). This was followed by four conditioning sessions during which the levers were removed and the rats were exposed to pairings of the lights-off stimulus with food. This phase was followed by two test sessions during which the levers were present and the number of responses made on each lever was calculated as a ratio of the number of responses made during the preexposure phase. A group receiving saline during the test sessions showed a higher ratio of responding for the lights off stimulus than the tone stimulus, demonstrating that the lights-off stimulus had become a conditioned reward. Amphetamine [2.0 mg/kg, intraperitoneally (i.p.), 5 min before the test] enhanced responding specifically on the lever producing the conditioned reward. Groups receiving SKF 38393 (5.0, 10.0, and 20.0 mg/kg, i.p., 5 min before the test) failed to show significantly greater responding for the lights-off stimulus than the tone, indicating a reduction or elimination of the conditioned reward effect. Moreover, SKF 38393 dose dependently reduced the amphetamine-produced enhancement of responding for conditioned reward.(ABSTRACT TRUNCATED AT 250 WORDS)