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.
Steinfels
G F
GF
E.I. du Pont de Nemours & Co., Inc., Medical Products Department, Wilmington, DE 19880-0400.
Tam
S W
SW
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000378:metabolism; D008839:Microelectrodes; D009292:Narcotic Antagonists; D009294:Narcotics / Q000494:pharmacology*; D009474:Neurons / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology*; D017465:Receptors, Opioid, delta; D013134:Spiperone / Q000378:metabolism
D014150:Antipsychotic Agents; D009292:Narcotic Antagonists; D009294:Narcotics; D010880:Piperidines; D011743:Pyrimidines; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; C050408:alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol; D013134:Spiperone; C026539:preclamol; D004298:Dopamine