Dopamine D1-like receptor agonists impair responding for conditioned reward in rats.

The dopamine (DA) D1-like receptor agonist SKF 38393 has been reported to impair responding for conditioned reward. SKF 38393 is a partial agonist and it is possible that the impairment occurred because it prevented endogenous DA from having its full impact on the D1-like receptor. The present experiments evaluated this possibility by examining the effects of several D1-like agonists with differing efficacy at stimulating adenylate cyclase. Male rats (n = 203) were trained in a procedure with three distinct phases. During the pre-exposure phase the rats were exposed for five 40min sessions to an operant chamber containing two levers; one produced a lights-off and the other a tone stimulus (3s). This was followed by the conditioning phase, four sessions during which the levers were removed and the rats received pairings of the lights-off stimulus (80 per day) with food, presented according to a variable time 45s schedule. The test phase included two 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 pre-exposure. Drugs were administered prior to each test session. No-injection and saline groups showed a higher ratio of responding for the lights-off than the tone stimulus, indicating that the lights-off stimulus had become a conditioned reward. The full D1-like agonist SKF 82958 (0.01-1.0mg/kg, s.c.) and the partial agonists SKF 81297 (0.01-1.0mg/kg), SKF 77434 (0.01-5.0mg/kg) and CY 208-243 (0.01-1.0mg/kg) impaired responding for conditioned reward at one or more of the highest doses. Results suggest that the impairments previously seen with SKF 38393 are not attributable to the partial agonist action of that drug, and continue to support the hypothesis that responding for conditioned reward is dependent on a reward-related DA signal at the D1-like receptor.