Interaction of opiates with dopamine receptors: receptor binding and behavioral assays.

We examined the hypothesis that opiates act as dopamine (DA) receptor-blocking agents thereby inducing a compensatory increase in DA receptor density during chronic administration, and that increased receptor density could account for the behavioral hypersensitivity to DA agonists seen after treatment with opiates. Morphine and methadone did not inhibit the specific binding of 3H-spiroperidol to DA receptors in vitro, nor did they decrease affinity or apparent receptor density in the striatum when administered acutely in vivo in behaviorally effective doses. In contrast, neuroleptics had the expected inhibitory effect in both these experiments. Stereotypy and locomotion in response to apomorphine were measured before and after a 3-week treatment with saline or methadone. About half the methadone-treated rats showed significant increases over predrug baselines in stereotypy or locomotion, as did a few saline-treated animals. However, in those animals showing enhanced stereotypy or locomotion, DA receptor density was not elevated in striatum or mesolimbic areas respectively. These results indicate that opiates do not act as antagonists at DA receptor sites, and that changes in DA receptor density cannot account for opiate-induced behavioral hypersensitivity.