Modafinil-Induced Conditioned Place Preference via Dopaminergic System in Mice

Modafinil, a psychostimulant, is used in the treatment of narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea. Preclinical and clinical studies suggest that modafinil may have reinforcing effects. However, a possible rewarding property of modafinil has not been fully investigated. In this study, we assessed the potential rewarding property of modafinil using the conditioned place preference (CPP) paradigm in mice. Using radiolabeled ligands, we observed changes in dopamine, glutamate, and GABA receptor binding in the brains of mice after treatment with modafinil. Modafinil produced significant CPP in mice at an intraperitoneal (i.p.) dose of 125 mg kg(-1) and prevented normal body weight gain of mice in a dose-dependent manner. A significant reduction in normal body weight gain was observed when mice were administrated 125 mg kg(-1) modafinil. In addition, there were widespread changes in receptor binding in the brains of modafinil-treated mice; Dopamine D(1) binding was increased in the caudate putamen, the accumbens, and the substantia nigra, while dopamine D(2) binding was decreased in the caudate putamen and the accumbens. Dopamine transporter (DAT) binding was increased in the prefrontal cortex, the caudate putamen, and the nucleus accumbens. No changes were observed in NMDA and GABAA receptor binding. These data indicate that modafinil had a significant rewarding property and could be abused as a recreational drug. Dopamine systems may play a key role in the rewarding property of modafinil. Synapse 65:733-741, 2011. (C) 2010 Wiley-Liss, Inc.