title: Methamphetamine-elicited alterations of dopamine- and serotonin-metabolite levels within mu-opioid receptor knockout mice: a microdialysis study.
abstract: mu-Opioid receptors (mu-ORs) modulate methamphetamine (MA)-induced behavioral responses, increased locomotor activity and stereotyped behavior in the mouse model. We investigated the changes in dopamine (DA) and serotonin (5-HT) metabolism in the striatum following either acute or repeated MA treatment using in vivo microdialysis. We also studied the role of mu-ORs in the modulation of MA-induced DA and 5-HT metabolism within mu-OR knockout mice. Subsequent to either acute or repeated intraperitoneal administration of MA, wild-type mice revealed decreases in extracellular concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in a dose-dependent manner. Moreover, wild-type mice had reductions in basal concentrations of DOPAC and HVA following repeated MA treatment with a higher dose. The effects of acute, repeated or challenge MA administration upon extracellular levels of DOPAC and HVA within mu-OR knockout mice significantly differed from the wild-type controls. The duration of recovery to the basal levels of extracellular DA and 5-HT metabolites induced by MA were much longer in wild-type mice than for mu-OR knockout mice. These findings suggest that mu-ORs play a modulatory role in MA-induced DA and 5-HT metabolism in the mouse striatum. This possible mechanism of MA-induced behavioral change as modulated by mu-OR merits further study.
authors.affiliation: Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kong Road, Taipei, 114, Taiwan, ROC.
authors.forename: Kuo-Cheng
authors.initials: KC
authors.lastname: Lan
authors.forename: Tangeng
authors.initials: T
authors.lastname: Ma
authors.forename: Shoei-Yn
authors.initials: SY
authors.lastname: Lin-Shiau
authors.forename: Shing-Hwa
authors.initials: SH
authors.lastname: Liu
authors.forename: Ing-Kang
authors.initials: IK
authors.lastname: Ho
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D017551:Microdialysis; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*
chemical_list: D017450:Receptors, Opioid, mu; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D008694:Methamphetamine; D006897:Hydroxyindoleacetic Acid; D004298:Dopamine; D006719:Homovanillic Acid