Selective sigma receptor agonist and antagonist affect dopamine neuronal activity.

Extracellular recording techniques were used to study the effects of the selective sigma receptor agonist (+)-[3H]3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP) and selective sigma receptor antagonist BMY 14802 on dopamine (DA) neurons of the substantia nigra. Intravenous administration of (+)-3-PPP produced a dose-dependent inhibition of DA neuron firing rate. Complete inhibition of DA neurons produced by (+)-3-PPP could be completely reversed by administration of BMY 14802. Also, pretreatment with BMY 14802 shifted the (+)-3-PPP dose response curve to the right. These data demonstrate a relationship of the sigma receptor with the dopamine system and further suggest a model system to study agonist/antagonist interactions of sigma ligands.