期刊
DRUG ADDICTION: RESEARCH FRONTIERS AND TREATMENT ADVANCES
卷 1139, 期 -, 页码 164-171出版社
WILEY-BLACKWELL
DOI: 10.1196/annals.1432.001
关键词
methamphetamine; apoptosis; 3-nitrotyrosine; nitric oxide synthase; neurokinin-1 receptor; striatum
资金
- National Institute on Drug Abuse [R01 DA020142]
- Research Centers in Minority Institutions
- NATIONAL INSTITUTE ON DRUG ABUSE [R01DA020142] Funding Source: NIH RePORTER
- National Institute on Minority Health and Health Disparities [G12MD007599] Funding Source: NIH RePORTER
Methamphetamine (METH) is a widely used club drug that produces neural damage in the brain, including the loss of some neurons. METH-induced striatal neuronal loss has been attenuated by pretreatment with the neurokinin-1 receptor antagonist WIN-51,708 in mice. Using a histologic method, we have observed the internalization of the neurokinin-1 receptor into endosomes in the striatal somatostatin/NPY/nitric oxide synthase interneurons. To investigate the role of this interneuron in the striatal cell death induced by METH, we assessed by immunohistochemistry the number of striatal nitric oxide synthase-positive neurons in the presence of METH at 8 and 16 hours after systemic injection of a bolus of METH (30 mg/kg, i.p.). We found the number of striatal nitric oxide synthase-positive neurons unchanged at these time points after METH. In a separate experiment we measured the levels of striatal 3-nitrotyrosine (3-NT) by HPLC (high-pressure liquid chromatography) as an indirect index of nitric oxide synthesis. METH increased the levels of 3-nitrotyrosine in the striatum and this increase was significantly attenuated by pretreatment with a selective neurokinin-1 receptor antagonist. These observations suggest a causal relationship between the neurokinin-1 receptor and the activation of neuronal nitric oxide synthase that warrants further investigation.
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