title: Chronic modafinil effects on drug-seeking following methamphetamine self-administration in rats.
abstract: Acute administration of the cognitive enhancing drug, modafinil (Provigil®), reduces methamphetamine (Meth) seeking following withdrawal from daily self-administration. However, the more clinically relevant effects of modafinil on Meth-seeking after chronic treatment have not been explored. Here, we determined the impact of modafinil on Meth-seeking after chronic daily treatment during extinction or abstinence following Meth self-administration. Rats self-administered intravenous Meth during daily 2-h sessions for 14 d, followed by extinction sessions or abstinence. During this period, rats received daily injections of vehicle, 30, or 100 mg/kg modafinil and were then tested for Meth-seeking via cue, Meth-primed, and context-induced reinstatement at early and late withdrawal time-points. We found that chronic modafinil attenuated relapse to a Meth-paired context, decreased conditioned cue-induced and Meth-primed reinstatement, and resulted in enduring reductions in Meth-seeking even after discontinuation of treatment. Additionally, we determined that only a very high dose of modafinil (300 mg/kg) during maintenance of self-administration had an impact on Meth intake. These results validate and extend clinical and preclinical findings that modafinil may be a viable treatment option for Meth addiction.
authors: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA. reichel@musc.edu
authors: Carmela M
authors: CM
authors: Reichel
authors: Ronald E
authors: RE
authors: See
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D000077408:Modafinil; D051381:Rats; D020318:Rats, Long-Evans; D012054:Reinforcement, Psychology; D012646:Self Administration; D013997:Time Factors
chemical_list: D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D000077408:Modafinil