Connection between the striatal neurokinin-1 receptor and nitric oxide formation during methamphetamine exposure.
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.
Wang
Jing
J
Department of Biological Sciences, Hunter College of the City University of New York, New York, New York, USA.
Xu
Wenjing
W
Ali
Syed F
SF
Angulo
Jesus A
JA
D000731:Androstanes / Q000378:metabolism; D000818:Animals; D001562:Benzimidazoles / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000378:metabolism / Q000648:ultrastructure; D004789:Enzyme Activation; D020287:In Situ Nick-End Labeling; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D064729:Neurokinin-1 Receptor Antagonists; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*
D000731:Androstanes; D001562:Benzimidazoles; D015259:Dopamine Agents; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; C086111:WIN 51708; D009569:Nitric Oxide; D008694:Methamphetamine; D052248:Nitric Oxide Synthase Type I