Characterization of phencyclidine-induced effects on neuropeptide Y systems in the rat caudate-putamen.
Multiple administrations of the psychotomimetic drug, phencyclidine-HCI (PCP), decreased striatal neuropeptide Y-like immunoreactivity (NPY-LI) levels in a dose-dependent manner. Single or multiple PCP administrations decreased striatal NPY levels after 10-12 h; levels returned to control 24 h after a single dose or 58 h after multiple doses. In contrast, no significant changes were seen in nigral NPY levels with either acute or multiple-dose PCP treatments. The role of monoamine, sigma or opioid receptors in PCP-induced striatal NPY changes was evaluated. When administered alone, the alpha 1-adrenergic antagonist, prazosin, the sigma antagonist, BMY 14802, and the dopamine D2 antagonist, sulpiride decreased striatal NPY levels; however, only prazosin and the dopamine D1 antagonist, SCH 23390, significantly attenuated PCP-induced changes. Administration of the gamma-aminobutyric acid transaminase (GABA-T) inhibitors, amino-oxyacetic acid (AOAA) or gamma-vinyl-GABA (GVG, vigabatrin, MDL 71,754) alone had no effect on striatal NPY-LI levels while administration of these indirect GABA agonists prior to or concurrently with PCP treatment completely blocked PCP-induced changes in striatal NPY-LI levels. The effect of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, on striatal NPY-LI content resembled that of PCP and was also blocked by the two indirect GABA agonists. These data suggest that NPY systems are modulated by glutamatergic activity (specifically by the NMDA receptor) and that the interaction between these two transmitter systems is mediated by GABAergic mechanisms.
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112.
L P
LP
Midgley
L G
LG
Bush
J W
JW
Gibb
G R
GR
Hanson
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000614:Aminocaproates / Q000494:pharmacology; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004146:Dioxanes / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019329:Idazoxan; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009478:Neuropeptide Y / Q000378:metabolism*; D010622:Phencyclidine / Q000008:administration & dosage / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000494:pharmacology; D011699:Putamen / Q000187:drug effects* / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000502:physiology; D013997:Time Factors; D020888:Vigabatrin
D000319:Adrenergic beta-Antagonists; D000614:Aminocaproates; D001552:Benzazepines; D002227:Carbazoles; D004146:Dioxanes; D009478:Neuropeptide Y; D011619:Psychotropic Drugs; D011743:Pyrimidines; D017450:Receptors, Opioid, mu; C050408:alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol; D000625:Aminooxyacetic Acid; D009270:Naloxone; D016291:Dizocilpine Maleate; C034931:rimcazole; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin; D010622:Phencyclidine; D011224:Prazosin; D019329:Idazoxan