DOPAMINE D-1 AND D-2 ANTAGONISTS ATTENUATE AMPHETAMINE-PRODUCED ENHANCEMENT OF RESPONDING FOR CONDITIONED REWARD IN RATS

It has been suggested that the dopamine D-1 receptor may play an important role in reward. The present study was undertaken to investigate the roles of dopamine D-1 and D-2 receptor subtypes in responding for conditioned reward. This was done by examining the effects of the D-1 antagonist SCH 23390 and the D-2 antagonists pimozide and metoclopramide on amphetamine-produced enhancement of responding for conditioned reward. The procedure consisted of three distinct phases. During the pre-exposure phase 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 was calculated as a ratio of the number of responses made during the pre-exposure phase. A group receiving the vehicle during the test sessions showed a greater ratio of responding for the lights-off stimulus than the tone stimulus, indicating that the lights-off stimulus had become a conditioned reward. Amphetamine (0.1, 1.0, 2.0 and 5.0 mg/k,IP, 5 min prior to test) specifically enhanced responding on the lever producing conditioned reward. SCH 23390 (5.0 and 10.0 mu g/ kg, SC, 2 h before test) and pimozide (0.1 and 0.2 mg/kg, IP, 4 h before test) dose-dependently shifted the peak in the amphetamine dose-response function to the right, indicating an attenuation of conditioned reward. Metoclopramide (1.0, 5.0 and 7.5 mg/kg, IP, 1 h before test) reduced the amphetamine-produced enhancement of responding for conditioned reward but failed to shift the amphetamine dose-response function. These results provide evidence that both D-1 and D-2 receptor subtypes are essential in responding for conditioned reward.