Phencyclidine and dizocilpine modulate dopamine release from rat nucleus accumbens via sigma receptors.
Phencyclidine (PCP) binds to many sites in brain, including PCP receptors located within the N-methyl-D-aspartate (NMDA) receptor-operated cation channel and sigma (sigma) receptors. In this study, we compare mechanisms by which PCP, dizocilpine (MK-801), the prototypical sigma receptor agonist (+)-pentazocine, and the proposed endogenous sigma receptor ligand neuropeptide Y regulate potassium (K(+))-stimulated [3H]dopamine release from slices of rat nucleus accumbens. (+)-Pentazocine inhibits K(+)-stimulated [3H]dopamine release, and neuropeptide Y enhances it. Both effects are blocked by sigma(1) and neuropeptide Y receptor antagonists, suggesting possible inverse agonism at a subpopulation of sigma/neuropeptide Y receptors. In contrast, PCP and MK-801 both enhance K(+)-stimulated [3H]dopamine release via sigma(1) and sigma(2) receptor subtypes, as demonstrated by antagonist sensitivity. Regulation of release by both (+)-pentazocine and neuropeptide Y persists in the presence of tetrodotoxin suggests that the sigma/neuropeptide Y receptors mediating the modulation are located presynaptically on dopaminergic nerve terminals, but tetrodotoxin eliminates regulation by PCP and MK-801, suggesting that receptors mediating their effects are located upstream from dopaminergic nerve terminals.
Ault
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Neuroscience Program, The George Washington University Medical Center, Washington, DC 20037, USA.
Werling
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D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D009478:Neuropeptide Y / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D010423:Pentazocine / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D009292:Narcotic Antagonists; D009478:Neuropeptide Y; D017480:Receptors, sigma; D016291:Dizocilpine Maleate; D010622:Phencyclidine; D010423:Pentazocine; D011188:Potassium; D004298:Dopamine