title: Modulation of methamphetamine-induced nitric oxide production by neuropeptide Y in the murine striatum.
abstract: Methamphetamine (METH) is a potent stimulant that induces both acute and long-lasting neurochemical changes in the brain including neuronal cell loss. Our laboratory demonstrated that the neuropeptide substance P enhances the striatal METH-induced production of nitric oxide (NO). In order to better understand the role of the striatal neuropeptides on the METH-induced production of NO, we used agonists and antagonists of the NPY (Y1R and Y2R) receptors infused via intrastriatal microinjection followed by a bolus of METH (30 mg/kg, ip) and measured 3-NT immunofluorescence, an indirect index of NO production. One striatum received pharmacological agent while the contralateral striatum received aCSF and served as control. NPY receptor agonists dose dependently attenuated the METH-induced production of striatal 3-NT. Conversely, NPY receptor antagonists had the opposite effect. Moreover, METH induced the accumulation of cyclic GMP and activated caspase-3 in approximately 18% of striatal neurons, a phenomenon that was attenuated by pre-treatment with NPY2 receptor agonist. Lastly, METH increased the levels of striatal preproneuropeptide Y mRNA nearly five-fold 16 h after injection as determined by RT-PCR, suggesting increased utilization of the neuropeptide. In conclusion, NPY inhibits the METH-induced production of NO in striatal tissue. Consequently, production of this second messenger induces the accumulation of cyclic GMP and activated caspase-3 in some striatal neurons, an event that may precede the apoptosis of some striatal neurons.
authors.affiliation: Hunter College of the City University of New York, Department of Biological Sciences, 695 Park Avenue, 10021 New York, NY, USA.
authors.forename: Haley L
authors.initials: HL
authors.lastname: Yarosh
authors.forename: Jesus A
authors.initials: JA
authors.lastname: Angulo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D004347:Drug Interactions; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D008845:Microinjections; D009478:Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: C092926:BIBP 3226; D009478:Neuropeptide Y; D010455:Peptides; D011498:Protein Precursors; D012333:RNA, Messenger; D017476:Receptors, Neuropeptide Y; C002744:3-nitrotyrosine; D014443:Tyrosine; D008694:Methamphetamine; C042084:preproneuropeptide Y; D001120:Arginine; D052247:Nitric Oxide Synthase Type II; D053148:Caspase 3; D006152:Cyclic GMP