Regulation of neuropeptide Y-containing neurons in the basal ganglia and limbic system of the rat;
Single or multiple administrations of the psychotomimetic drug, phencyclidine-HCl (PCP), decreased striatal, cortical and accumbens, but not nigral, neuropeptide Y-like immunoreactivity (NPYLI) levels at some time point(s) after administration. The effect of the noncompetitive NMDA receptor antagonist, MK-801, on striatal, cortical and accumbens NPYLI content was similar to PCP, suggesting that extrapyramidal and limbic NPY systems are modulated by glutamatergic activity through NMDA receptor mechanisms. Administration of the GABA-T inhibitors, amino-oxyacetic acid (AOAA) or gamma-vinyl-GABA (GVG) alone had no effect on striatal or cortical NPYLI levels; however, AOAA administration alone decreased accumbens NPYLI levels. Administration of AOAA or GVG prior to or concurrently with PCP treatment completely blocked PCP-induced changes in striatal and cortical NPYLI levels while accumbens NPYLI changes were attenuated. These data suggest that striatal, cortical and accumbens NPY systems are modulated by glutamatergic activity and that the interaction between these two transmitter systems is mediated, at least in part, by GABAergic mechanisms. The role of dopamine (DA) and several other transmitter or receptor systems in PCP-induced extrapyramidal and limbic NPYLI changes was also evaluated. Neither the dopamine D-1 receptor, SCH 23390, nor the dopamine D-2 antagonist, sulpiride, by themselves altered cortical NPY systems but in combination they totally blocked the PCP-induced changes. In contrast, sulpiride alone significantly reduced striatal and accumbens NPYLI content and enhanced the PCP-induced decreases, while SCH 23390 alone had no effect on striatal and accumbens NPYLI levels but did attenuate PCP-induced effects. These data suggest that basal ganglia and limbic NPY systems are differentially modulated by NMDA and dopaminergic activity. Examination of the effects of multiple administrations of selective D-1 and D-2 agonists and antagonists on striatal, nigral, accumbens, pallidal and cortical NPY systems indicated that within structures such as the caudate and nucleus accumbens there exists multiple distinct NPY systems which are uniquely influenced by DA receptors. Initial studies suggest that both GABA-A and -B receptors are involved in mediating the PCP-induced NPYLI changes, and that PCP causes both release of NPY from nerve terminals and increased peptide biosynthesis.
University of Utah
Phencyclidine; Neuropeptide Y; Basal Ganglia;
University of Utah;
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Digital reproduction of “Regulation of neuropeptide Y-containing neurons in the basal ganglia and limbic system of the rat Spencer S. Eccles Library.