title: Modafinil-induced conditioned place preference via dopaminergic system in mice.
abstract: 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 D₁ binding was increased in the caudate putamen, the accumbens, and the substantia nigra, while dopamine D₂ 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 GABA(A) 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.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Thi-Lien
authors.initials: TL
authors.lastname: Nguyen
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Tian
authors.forename: In-Jee
authors.initials: IJ
authors.lastname: You
authors.forename: Seok-Yong
authors.initials: SY
authors.lastname: Lee
authors.forename: Choon-Gon
authors.initials: CG
authors.lastname: Jang
mesh_terms: D000818:Animals; D001345:Autoradiography; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D000077408:Modafinil; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism
chemical_list: D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D000077408:Modafinil; D004298:Dopamine