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  • Title: Electrophysiological effects of selective sigma-receptor agonists, antagonists, and the selective phencyclidine receptor agonist MK-801 on midbrain dopamine neurons.
    Author: Steinfels GF, Tam SW, Cook L.
    Journal: Neuropsychopharmacology; 1989 Sep; 2(3):201-8. PubMed ID: 2571340.
    Abstract:
    Extracellular single unit recording techniques were used to study the effects of selective sigma-receptor agonist [(+)-3-PPP, (+)-pentazocine, and DTG] and selective sigma-receptor antagonists (BMY 14802 and Rimcazole) on dopamine neurons of the substantia nigra. Intravenous (IV) administration of sigma agonists decreased, whereas IV administration of the sigma antagonist BMY-14802 increased the firing rate of dopamine neurons. The other sigma antagonist Rimcazole produced inconsistent changes in dopamine unit activity. These data, in conjunction with anatomic data suggesting sigma receptor localization on dopamine neurons in the substantia nigra (Gundlach et al: J Neurosci 6:1757-1770, 1986; Graybiel et al: Soc Neurosci Abstr 13:28, 1987) 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. The selective phencyclidine (PCP) agonist MK-801 was equipotent to PCP in regard to stimulatory properties on dopamine neurons. However, the relative potencies do not correspond to their relative binding affinities, suggesting that non-PCP-receptor properties may mediate this effect.
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