Affinity for the dopamine D2 receptor predicts neuroleptic potency in blocking the reinforcing effect of MFB stimulation.

For each of nine neuroleptics, the dose required to block sustained responding for intracranial stimulation of the medial forebrain bundle was determined in the rat. To check whether the blocking of responding was due to effects on reinforcement as opposed to effects on performance factors, the rats were always tested for task-specific extinction of responding by transferring them to another testing box once they refused to respond in the first testing box. With all the neuroleptics, task-specific extinction was seen in at least some of the animals. Task-specific extinction was not seen in control tests with a general anaesthetic (Chloropent) nor with picrotoxin, a drug that can produce pseudo-extinction. Affinity for the dopamine D2 receptor (from in vitro studies) predicted neuroleptic potency in blocking reinforcement, whereas affinity for other aminergic receptors (D1, D3, the alpha-adrenergic receptor, S1, and S2) did not.