Differential regulation of neuropeptide Y systems in limbic structures of the rat.
Neuropeptide Y-like immunoreactivity (NPYLI) in the frontal cortex and nucleus accumbens was significantly decreased after acute and multiple administrations of phencyclidine-HCl (PCP). The role of dopamine, serotonin and sigma receptors in these PCP-induced effects was evaluated. Neither the dopamine D1 antagonist SCH 23390 nor the D2 antagonist sulpiride by itself altered cortical neuropeptide systems, but in combination they totally blocked the PCP-induced changes. In contrast, sulpiride alone significantly decreased accumbens NPYLI content and enhanced the PCP-induced decreases, whereas SCH 23390 alone had no effect on accumbens NPYLI levels but did attenuate PCP-induced effects. Neither depletion of serotonin nor blockage of the sigma "receptor" had any effect on PCP-induced changes in either structure. The effects of the selective, noncompetitive N-methyl-D-aspartate receptor antagonist MK-801 on cortical and accumbens NPYLI content were similar to those of PCP, suggesting an N-methyl-D-aspartate receptor mechanism in these effects. Administration of gamma-aminobutyric acid-transaminase (GABA-T) inhibitors, gamma-vinyl-GABA (GVG, vigabatrin, MDL 71,754) or aminooxyacetic acid alone had no effect on cortical NPYLI content; however, administration of aminooxyacetic acid alone decreased accumbens NPYLI levels. Co-administration of these GABA-T inhibitors with PCP completely blocked PCP-induced cortical NPYLI decreases and attenuated NPYLI changes in the accumbens. These data suggest that limbic neuropeptide systems are differentially modulated by N-methyl-D-aspartate and dopaminergic activity and that glutamatergic influences on cortical and accumbens NPY systems are mediated, at least in part, by GABAergic mechanisms.
Midgley
L P
LP
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City.
Bush
L G
LG
Gibb
J W
JW
Hanson
G R
GR
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009478:Neuropeptide Y / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010622:Phencyclidine / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D017480:Receptors, sigma / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000172:deficiency; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D065127:Dopamine D2 Receptor Antagonists; D009478:Neuropeptide Y; D017447:Receptors, Dopamine D1; D017480:Receptors, sigma; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D016291:Dizocilpine Maleate; D010622:Phencyclidine