Methamphetamine induces striatal neurokinin-1 receptor endocytosis primarily in somatostatin/NPY/NOS interneurons and the role of dopamine receptors in mice.
Methamphetamine (METH) is a psychostimulant that induces long-term deficits of dopamine terminal markers and apoptotic cell death in the striatum. Our laboratory demonstrated that pharmacological blockade of the neurokinin-1 receptor attenuated the METH-induced damage to the striatal dopamine terminals and the apoptotic cell death of some striatal neurons. Here, we used histological methods to assess the effect of METH on neurokinin-1 receptor trafficking in the striatum as an indirect index of signaling by the neuropeptide substance P (natural ligand for this receptor). Male mice received a single injection of METH (30 mg/kg, i.p.) and were sacrificed 30 min later. Immunohistofluorescence confocal microscopy confirmed that the neurokinin-1 receptor is located on cholinergic and somatostatin interneurons of the striatum. METH induced the trafficking of the neurokinin-1 receptor from the membrane into cytoplasmic endosomes primarily in the somatostatin/NPY/NOS interneurons, and this phenomenon was attenuated by antagonists of the dopamine D1 (SCH-23390), D2 (raclopride), or neurokinin-1 (WIN-51,708) receptors. These data demonstrate that METH induces the trafficking of the striatal neurokinin-1 receptors principally in the somatostatin/NPY/NOS interneurons and that this phenomenon is dependent on the activity of dopamine D1 and D2 receptors.
Wang
Jing
J
Department of Biological Sciences, Hunter College of the City University of New York, New York, New York 10021, USA.
Angulo
Jesus A
JA
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D007395:Interneurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D009478:Neuropeptide Y / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000502:physiology*; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism*
D018492:Dopamine Antagonists; D009478:Neuropeptide Y; D011954:Receptors, Dopamine; D018040:Receptors, Neurokinin-1; D008694:Methamphetamine; D013004:Somatostatin; D019001:Nitric Oxide Synthase