title: Protective effects of minocycline on behavioral changes and neurotoxicity in mice after administration of methamphetamine.
abstract: The effects of minocycline on behavioral changes and neurotoxicity in the dopaminergic neurons induced by the administration of methamphetamine (METH) were studied. Pretreatment with minocycline (40 mg/kg) was found to attenuate hyperlocomotion in mice after a single administration of METH (3 mg/kg). The development of behavioral sensitization after repeated administration of METH (3 mg/kg/day, once daily for 5 days) was significantly attenuated by pretreatment with minocycline (40 mg/kg). A reduction in the level of dopamine (DA) and its major metabolite, 3,4-dihydroxyphenyl acetic acid (DOPAC), in the striatum after the repeated administration of METH (3 mg/kg x 3, 3-h interval) was attenuated in a dose-dependent manner by pretreatment with and the subsequent administration of minocycline (10, 20, or 40 mg/kg). Furthermore, minocycline (40 mg/kg) significantly attenuated a reduction in DA transporter (DAT)-immunoreactivity in the striatum after repeated administration of METH. In vivo microdialysis study demonstrated that pretreatment with minocycline (40 mg/kg) significantly attenuated increased extracellular DA levels in the striatum after the administration of METH (3 mg/kg). In addition, minocycline was not found to alter the concentrations of METH in the plasma or the brain after three injections of METH (3 mg/kg), suggesting that minocycline does not alter the pharmacokinetics of METH in mice. Interestingly, METH-induced neurotoxicity in the striatum was significantly attenuated by the post-treatment and subsequent administration of minocycline (40 mg/kg). These findings suggest that minocycline may be able to ameliorate behavioral changes as well as neurotoxicity in dopaminergic terminals after the administration of METH. Therefore, minocycline could be considered as a useful drug for the treatment of several symptoms associated with METH abuse in humans.
authors.affiliation: Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chiba 260-8670, Japan.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Kiyoyuki
authors.initials: K
authors.lastname: Kitaichi
authors.forename: Yohei
authors.initials: Y
authors.lastname: Fujimoto
authors.forename: Hironao
authors.initials: H
authors.lastname: Nakayama
authors.forename: Eiji
authors.initials: E
authors.lastname: Shimizu
authors.forename: Masaomi
authors.initials: M
authors.lastname: Iyo
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008911:Minocycline / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects*; D009068:Movement / Q000187:drug effects / Q000502:physiology; D019966:Substance-Related Disorders / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D008694:Methamphetamine; D008911:Minocycline