TY - JOUR T1 - Effects of Hydroxymetabolites of Bupropion on Nicotine Dependence Behavior in Mice JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1087 LP - 1095 DO - 10.1124/jpet.110.166850 VL - 334 IS - 3 AU - M. Imad Damaj AU - Sheri D. Grabus AU - Hernan A. Navarro AU - Robert E. Vann AU - Jonathan A. Warner AU - Lindsey S. King AU - Jenny L. Wiley AU - Bruce E. Blough AU - Ronald J. Lukas AU - F. Ivy Carroll Y1 - 2010/09/01 UR - http://jpet.aspetjournals.org/content/334/3/1087.abstract N2 - Bupropion is an atypical antidepressant that also has utility as a smoking cessation aid. Hydroxybupropions are major metabolites of bupropion and are believed to contribute to antidepressant and perhaps smoking cessation activities. Because bupropion metabolism is more similar in humans and mice than in humans and rats, the present study investigated effects of hydroxybupropion enantiomers in mouse behavioral models measuring various aspects of nicotine dependence. Bupropion and (2S,3S)-hydroxybupropion, but not (2R,3R)-hydroxybupropion, significantly decreased the development of nicotine reward as measured in the conditioned place preference and withdrawal paradigm in mice. Bupropion and both of its metabolites reversed affective and somatic withdrawal signs in nicotine-dependent mice, but the (2S,3S)-hydroxymetabolite had higher potency. Bupropion and (2S,3S)-, but not (2R,3R)-hydroxybupropion, produced partial substitution for nicotine in drug discrimination tests. Our findings support the hypothesis that the effects of bupropion on measures of nicotine dependence reflect actions of bupropion itself, its hydroxymetabolites, or a combination and suggest that the (2S,3S)-hydroxy isomer is the most active principle, making it a potentially better drug candidate for smoking cessation than bupropion. ER -