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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.

SUBMITTER: Reichel CM

PROVIDER: S-EPMC3258466 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Chronic modafinil effects on drug-seeking following methamphetamine self-administration in rats.

Reichel Carmela M CM See Ronald E RE

The international journal of neuropsychopharmacology 20110628 7

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 dai ...[more]

PMID: 21733228

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Project description:Background:Neurotensin is a peptide that modulates central dopamine neurotransmission and dopamine-related behaviors. Methamphetamine self-administration increases neurotensin levels in the ventral tegmental area, but the consequences for self-administration behavior have not been described. Here we test the hypothesis that antagonizing neurotensin receptors in the ventral tegmental area attenuates the acquisition of methamphetamine self-administration and methamphetamine intake. Methods:We implanted mice with an indwelling catheter in the right jugular vein and bilateral cannulae directed at the ventral tegmental area. Mice were then trained to nose-poke for i.v. infusions of methamphetamine (0.1 mg/kg/infusion) on a fixed ratio 3 schedule. Results:Mice receiving microinfusions of the neurotensin NTS1/NTS2 receptor antagonist SR142948A in the ventral tegmental area (10 ng/side) prior to the first 5 days of methamphetamine self-administration required more sessions to reach acquisition criteria. Methamphetamine intake was decreased in SR142948A-treated mice both during training and later during maintenance of self-administration. Drug seeking during extinction, cue-induced reinstatement, and progressive ratio schedules was also reduced in the SR142948A group. The effects of SR142948A were not related to changes in basal locomotor activity or methamphetamine psychomotor properties. In both SR142948A- and saline-treated mice, a strong positive correlation between methamphetamine intake and enhanced locomotor activity was observed. Conclusion:Our results suggest that neurotensin input in the ventral tegmental area during initial methamphetamine exposure contributes to the acquisition of methamphetamine self-administration and modulates later intake and methamphetamine-seeking behavior in mice. Furthermore, our results highlight the role of endogenous neurotensin in the ventral tegmental area in the reinforcing efficacy of methamphetamine, independent of its psychomotor effects.

Dataset Information

Chronic modafinil effects on drug-seeking following methamphetamine self-administration in rats.

Publications

Chronic modafinil effects on drug-seeking following methamphetamine self-administration in rats.

Similar Datasets

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