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Attenuated methamphetamine induced neurotoxicity by modafinil administration in mice.

Abstract
Methamphetamine (METH) is a highly addictive drug that might induce neurotoxicity. Clinical trials have reported that modafinil, a wake-promoting agent used to treat sleep disorders, may have some efficacy for the treatment of psychostimulant addiction. In this study we tested possible neuroprotective effects of modafinil after toxic METH administration in mice. We evaluated the effect of modafinil (two injections of either 90 or 180 mg/kg) and METH binge (3 × 7 mg/kg i.p. injections, 3-h apart) coadministration on DA striatal content, TH immunoreactivity in striatal areas and spontaneous locomotor activity. We also investigated acute locomotor activity and stereotypy profile in mice treated with a single METH dose (2 and 7 mg/kg) pretreated with modafinil (90 and 180 mg/kg). We found that mice treated with a METH binge showed a marked decrease in DA and dopaminergic metabolites as well as lower levels of TH immunoreactivity in the dorsal striatum. Pretreatment with modafinil (both 90 and 180 mg/kg) attenuated these effects but did not prevent METH induced decrease in locomotion. We also found that groups that received the combination of both modafinil and single dose METH showed a decrease in total distance traveled in an open field compared with METH groups. We observed an increment in the time mice expended doing stereotypic movements (continuous sniffing) in the group that received the combination of both METH and modafinil (i.e., decreasing locomotion). Our results suggest a possible protective role of modafinil against METH acute striatal toxicity.
AuthorsMariana Raineri, Viviana Peskin, Belén Goitia, Irene R E Taravini, Sergio Giorgeri, Francisco J Urbano, Verónica Bisagno
JournalSynapse (New York, N.Y.) (Synapse) Vol. 65 Issue 10 Pg. 1087-98 (Oct 2011) ISSN: 1098-2396 [Electronic] United States
PMID21590747 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Wiley-Liss, Inc.
Chemical References
  • Benzhydryl Compounds
  • Central Nervous System Stimulants
  • Neuroprotective Agents
  • Methamphetamine
  • modafinil
Topics
  • Amphetamine-Related Disorders (drug therapy)
  • Animals
  • Benzhydryl Compounds (pharmacology)
  • Central Nervous System Stimulants (toxicity)
  • Drug Administration Schedule
  • Drug Interactions
  • Male
  • Methamphetamine (toxicity)
  • Mice
  • Motor Activity (drug effects)
  • Neuroprotective Agents (pharmacology)
  • Stereotyped Behavior (drug effects)

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