Modafinil blocks reinstatement of extinguished opiate-seeking in rats: mediation by a glutamate mechanism.

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
Pouya Tahsili-FahadanGary Aston-Jones

Abstract

Opiate addiction is characterized by high rates of relapse even after long periods of abstinence, requiring new relapse-prevention treatments that do not have abuse potential. Recently, clinical studies suggested that the wake-promoting drug modafinil might decrease relapse in cocaine addicts. In addition, group II metabotropic glutamate receptors (mGlu2/3R) have been suggested as a new therapeutic target for drug addiction. Here, we investigated the ability of modafinil to prevent the acute morphine to promote reinstatement of extinguished preference for morphine, and the involvement of mGlu2/3Rs in this effect. Conditioned place preference (CPP) for morphine was induced in Sprague-Dawley rats, followed by extinction training. Preference for the morphine-paired side was reinstated following extinction by a morphine-priming injection. The results of our study showed that modafinil (300 mg/kg, i.p., but not 100 mg/kg) 30 min before the morphine-priming injection blocked reinstatement of extinguished CPP. The anti-reinstatement effect of modafinil was completely prevented by pretreatment with the selective mGlu2/3 antagonist LY341495. Additional experiments indicated that modafinil alone did not produce a preference, and that mod...Continue Reading

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Citations

Apr 27, 2011·Molecular Psychiatry·P W Kalivas, N D Volkow
Jul 28, 2011·Addiction Biology·Raphael Wuo-SilvaRoberto Frussa-Filho
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Mar 8, 2017·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Hai-Ying ZhangZheng-Xiong Xi
Dec 17, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Pouya Tahsili-FahadanGary Aston-Jones
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Jun 15, 2021·Frontiers in Neuroscience·Melinda HerseyGianluigi Tanda
Nov 9, 2017·ACS Chemical Neuroscience·Eric Murillo-RodríguezSérgio Machado

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