Modulation of methamphetamine-induced nitric oxide production by neuropeptide Y in the murine striatum
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- 作者：Haley L. Yarosh ; Jesus A. Angulo
- 关键词：aCSF ; artificial cerebrospinal fluid ; DARPP-32 ; dopamine and cyclic adenosine 3&prime ; 5&prime ; -monophosphate-regulated phosphoprotein ; 32 ; kDa ; ICR ; Institute for Cancer Research ; ip ; intraperitoneal ; METH ; (+)-methamphetamine hydrochloride ; NPY ; neu
- 刊名：Brain Research
- 出版年：2012
- 出版时间：5 November, 2012
- 年：2012
- 卷：1483
- 期：Complete
- 页码：31-38
- 全文大小：629 K
文摘
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.