The role of antagonism of NMDA receptor-mediated neurotransmission and inhibition of the dopamine reuptake in the neuroendocrine effects of phencyclidine.
Phencyclidine (PCP) activates the hypothalamo-pituitary-adrenal (HPA) axis and decreases plasma prolactin levels in the rat. PCP is a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, but it also inhibits the reuptake of dopamine, serotonin and norepinephrine. The purpose of the present study was to utilize the PCP analogue N-[1-(2-thienyl)cyclohexyl]piperidine; (TCP), the potent dopamine reuptake inhibitor N-[1-(2-benzo(b)thiophenyl) cyclohexyl]piperidine; (BTCP) and the nonselective monoamine reuptake inhibitor cocaine as pharmacologic probes in order to determine the roles of noncompetitive NMDA receptor blockade and inhibition of dopamine reuptake in the neuroendocrine effects of PCP. PCP, TCP and cocaine increased plasma levels of adrenocorticotropin and corticosterone, but BTCP had no effect. In contrast, PCP, BTCP and cocaine decreased plasma prolactin, but TCP produced no such effect. The data suggest that mechanisms besides inhibition of dopamine reuptake are involved in the effects of PCP on the HPA axis, and the PCP-induced decrease in plasma prolactin is not a consequence of inhibition of NMDA receptor-mediated neurotransmission.
Pechnick
Robert N
RN
Department of Psychiatry and Mental Health, Cedars-Sinai Medical Center, 8730 Alden Drive, Los Angeles, CA, 90048, USA. pechnickr@cshs.org
Bresee
Catherine J
CJ
Poland
Russell E
RE
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive; D003042:Cocaine / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D018491:Dopamine Agonists / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000494:pharmacology; D011388:Prolactin / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; C056415:1-(1-(2-benzo(b)thienyl)cyclohexyl)piperidine; C012058:tenocyclidine; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D003042:Cocaine; D010622:Phencyclidine; D003345:Corticosterone