Journal
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
Volume 30, Issue 8, Pages 1381-1393Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2006.05.015
Keywords
dopamine; methamphetamine; microdialysis; microglia; neurotoxicity; sensitization
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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. (c) 2006 Elsevier Inc. All rights reserved.
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