The monoamine oxidase (MAO) inhibitor tranylcypromine enhances nicotine self-administration in rats through a mechanism independent of MAO inhibition

NEUROPHARMACOLOGY

卷:61

Article

Lotfipour, Shahrdad¹  Arnold, Monica M.²  Hogenkamp, Derk J.²  Gee, Kelvin W.²  Belluzzi, James D.²  Leslie, Frances M.^1,2 

[1] Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92697 USA

[2] Univ Calif Irvine, Sch Med, Dept Pharmacol, Irvine, CA 92697 USA

关键词: Dopamine;    Microdialysis;    Monoamine oxidase;    Serotonin;    Stereoisomers;   

DOI  :  10.1016/j.neuropharm.2011.03.007

来源: Elsevier

【 摘 要 】

Our current study aims to evaluate the mechanisms of tranylcypromine (TCP)-mediated enhancement of nicotine self-administration. We replicated our previous findings which demonstrate that 1 h pretreatment with TCP (3 mg/kg, i.p.) enhances nicotine self-administration (7.5 mu g/kg/inj, i.v.) when compared with vehicle-treated rodents. We tested whether TCP-mediated enhancement of nicotine self-administration was due to MAO inhibition or off-target effects by (i) extending the TCP pretreatment time from 1 to 20 h, and (ii) evaluating the role of the individual TCP stereoisomers in nicotine self-administration studies. While 20 h and (-)TCP pretreatment induced significant inhibition of MAO (60-90%), animals found nicotine only weakly reinforcing. Furthermore, while both (+) and (+/-) TCP treatment induced nearly 100% MAO inhibition, (+)TCP pretreated animals took longer to acquire nicotine self-administration compared to (+/-)TCP pretreated animals. Stable nicotine self-administration in (+)TCP pretreated animals was influenced by nicotinic receptor activation but not nicotine-paired cues. The opposite was found in (+/-)TCP pretreated animals. Treatment with (-) or (+/-)TCP increased dopamine and serotonin overflow, while the (+) and (+/-)TCP treatment enhanced monoamine overflow subsequent to nicotine. Together, our data suggests TCP enhancement of nicotine self-administration are mediated through mechanisms independent of MAO inhibition, including nicotine-paired cues and monoamine uptake inhibition. (C) 2011 Elsevier Ltd. All rights reserved.

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