期刊
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
卷 95, 期 4, 页码 449-456出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2010.03.006
关键词
Modafinil; Locomotor sensitization; Drug discrimination; Cocaine; d-amphetamine; Bupropion; Citalopram; Desipramine; GBR12909; Caffeine; Rat; Mouse
资金
- NIMH NIH HHS [R43 MH078433-01A1, R43 MH078433] Funding Source: Medline
The present studies assessed the potential abuse liability and likely mechanism(s) of action of the wake-promoting agent modafinil. Methods: Experiments assessed the locomotor sensitization (LS) and discriminative stimulus (DS) properties of modafinil in mouse and rat, respectively. Comparative data were generated with a range of psychostimulants and monoamine reuptake inhibitors. Results: Repeated administration of d-amphetamine and cocaine, psychostimulants with high abuse liability, resulted in the induction and expression of LS in mice. Bupropion and caffeine, two psychostimulants not abused in humans, were not associated with LS. GBR12909 induced LS during repeated exposure, but there was no evidence of expression of LS after acute challenge following withdrawal. In contrast, repeated administration of modafinil resulted in the expression, but not induction, of LS. d-amphetamine, but not the p-opioid agonist morphine or the nAChR agonist nicotine, fully substituted for the cocaine DS in rats. The selective dopamine transporter (DAT) inhibitor GBR12909 fully substituted, the preferential norepinephrine transporter (NET) inhibitor desipramine partially substituted, and the selective serotonin reuptake inhibitor citalopram failed to substitute for cocaine. Modafinil fully substituted for cocaine, similar to the mixed DAT/NET inhibitor bupropion. Conclusions: Two preclinical assays indicated potential abuse liability of modafinil; drug discrimination studies suggest DAT blockade by modafinil is a likely mechanism of action in vivo. (C) 2010 Elsevier Inc. All rights reserved.
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