Psychotomimetic opiate receptors labeled and visualized with (+)-[³H]3-(3-hydroxyphenyl)-N-(1-propyl)piperidine

3-(3-Hydroxyphenyl)-N-(1-propyl)piperidine (3-PPP) has been proposed as a selective dopamine autoreceptor agonist in the central nervous system. This report describes the pharmacology and localization of specific high-affinity binding sites for (+)-[³H]3-PPP in brain. The drug specificity of (+)-[³H]3-PPP binding is identical to that of σ receptors, which may mediate psychotomimetic effects of some opiates. Haloperidol and the opioid derivatives, pentazocine, cyclazocine and SKF 10,047 are potent inhibitors of (+)-[³H]3-PPP binding. Stereoselectivity is exhibited for the (+) isomers of cyclazocine and SKF 10,047 at the σ site, opposite to the stereoselectivity seen at μ, δ, and κ opiate receptors. (+)-[³H]3-PPP does not label dopamine receptors, as potent dopamine agonists and antagonists are weak inhibitors of binding and the localization of specific (+)-[³H]3-PPP binding sites does not parallel that of dopamine neurons. Discrete localizations of (+)-[³H]3-PPP binding sites in many brain areas including limbic, midbrain, brainstem, and cerebellar regions may explain psychotomimetic actions of opiates and behavioral effects of 3-PPP.