D-1 receptor involvement in reward-related learning.

A comparison of the effects of apomorphine, amphetamine and dopamine (DA) receptor subtype-specific agonists in responding for conditioned reward, self-administration and place conditioning paradigms provides insights into the possible involvement of D-1 and D-2 receptors in reward-related learning. Amphetamine and the D-2 agonists bromocriptine and quinpirole enhanced responding for conditioned reward, were self-administered and produced place preferences. Apomorphine impaired responding for conditioned reward by enhancing responding on two levers, was self-administered and produced a place preference. The D-1 agonist SKF 38393 impaired responding for condition reward, did not support self-administration and produced a place preference. The failure of SKF 38393 to support self-administration may have been related to effects of this drug, for example, peripheral aversive effects or a slow onset of action, unrelated to its action at the D-1 receptor. It was suggested that a D-1 agonist might be expected to be self-administered from the point of view of the hypothesis that it is the action at D-1 receptors of DA released in association with reward that produces reward-related learning. This hypothesis was supported by the remaining data. Thus, apomorphine and SKF 38393 may have masked the DA signal associated with reward in the conditioned reward paradigm leading to a loss of control of responding by the conditioned rewarding stimulus. In self-administration, apomorphine would have its onset of action after the performance of the response which is followed immediately by a conditioned reward. The conditioned reward may effectively maintain control of behaviour by the lever and related stimuli while the drug may maintain the effectiveness of the conditioned reward. In place conditioning, there is no specific environmental stimulus that must come to control responding; therefore, apomorphine and SKF 38393 may have been seen to produce place preferences in spite of their relatively tonic action at D-1 receptors. Finally, the finding that the D-1 antagonists SCH 23390 or SCH 39166 blocked the effects of reward in these paradigms was taken as further evidence that the D-1 receptor may be critically involved in the learning produced by rewarding stimuli.