title: Naloxonazine, a specific mu-opioid receptor antagonist, attenuates the increment of locomotor activity induced by acute methamphetamine in mice.
abstract: Our previous studies indicated that the endogenous opioid system, particularly the mu-opioid receptor, may be involved in the modulation of methamphetamine (METH)-induced increases in locomotor behavior in mice. This study investigates the effects of naloxonazine, a specific mu-opioid receptor antagonist, on the locomotor behavioral response and phosphorylation pattern of dopamine and cAMP-regulated phosphoprotein of Mr32 (DARPP-32) in striatal dopaminergic transmissions induced by acute administration of METH to mice. Mice were injected with a single dose of naloxonazine (20 mg/kg, i.p.) 60 min before injecting (i.p.) either saline or 1 mg/kg of METH. After a 2-h behavioral test, striatal tissues were collected to determine the protein levels of DARPP-32 and the phosphorylated form of DARPP-32 at the Thr34 and Thr75 sites. Results show that pretreatment with naloxonazine significantly attenuated the acute METH-induced increase in locomotor activity and phosphor-Thr75 DARPP-32 levels. Our data indicate that the mu-opioid receptor blockade reduces the acute METH-induced increase in locomotor activity. This effect may be related to the inhibition of DARPP-32 phosphorylation at the Thr75 site in the striatum of the mice.
authors.affiliation: Department of Anesthesiology, Sijhih Cathay General Hospital, New Taipei City, Taiwan, ROC.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Chien
authors.forename: Yih-Jing
authors.initials: YJ
authors.lastname: Lee
authors.forename: Lir-Wan
authors.initials: LW
authors.lastname: Fan
authors.forename: Ing-Kang
authors.initials: IK
authors.lastname: Ho
authors.forename: Lu-Tai
authors.initials: LT
authors.lastname: Tien
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000037:antagonists & inhibitors / Q000378:metabolism; D004347:Drug Interactions; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects*; D009270:Naloxone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010766:Phosphorylation; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*; D014741:Video Recording
chemical_list: D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009270:Naloxone; D008694:Methamphetamine; C034643:naloxonazine; D004298:Dopamine