title: Differential action of methamphetamine on tyrosine hydroxylase and dopamine transport in the nigrostriatal pathway of μ-opioid receptor knockout mice.
abstract: Extensive anatomical and functional interactions exist between central dopaminergic and opioidergic systems and both systems are proposed to be targets for amphetamine-like drugs. We have previously reported that μ-opioid receptor (μ-OR) knockout mice are resistant to the loss of dopamine in the striatum and the development of behavioral sensitization induced by repeated methamphetamine (METH) treatment. The present study assessed whether METH-treated μ-OR knockout mice exhibit a differential response of the expression of dopamine transporter and tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine synthesis and maintaining dopamine levels. Mice daily received intraperitoneal injection of METH (0, 0.6, 2.5, or 10 mg/kg) for 7 days and sacrificed on day 11 (4 days after the last injection). The expression of TH protein in the striatum and the levels of TH mRNA and number of TH positive neurons in the substantia nigra were reduced in wild-type mice treated with METH (2.5 and 10 mg/kg), but not in the μ-OR knockout mice. In contrast, METH exposure at the highest dose (10 mg/kg) reduced dopamine transporter levels in both strains of mice. These results suggest that the μ-OR contributes to METH-induced loss of dopamine and behavioral sensitization by decreasing the expression of TH.
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA. spark@umc.edu
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Park
authors.forename: Zhi
authors.initials: Z
authors.lastname: He
authors.forename: Xine
authors.initials: X
authors.lastname: Shen
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Roman
authors.forename: Tangeng
authors.initials: T
authors.lastname: Ma
mesh_terms: D000818:Animals; D003042:Cocaine / Q000031:analogs & derivatives; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007457:Iodine Radioisotopes; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000502:physiology*; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D017450:Receptors, Opioid, mu; C079213:RTI 121; D008694:Methamphetamine; D014446:Tyrosine 3-Monooxygenase; D003042:Cocaine