title: The monoamine oxidase (MAO) inhibitor tranylcypromine enhances nicotine self-administration in rats through a mechanism independent of MAO inhibition.
abstract: 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 μg/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.
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, CA 92697, USA. shahrdad@ucla.edu
authors.forename: Shahrdad
authors.initials: S
authors.lastname: Lotfipour
authors.forename: Monica M
authors.initials: MM
authors.lastname: Arnold
authors.forename: Derk J
authors.initials: DJ
authors.lastname: Hogenkamp
authors.forename: Kelvin W
authors.initials: KW
authors.lastname: Gee
authors.forename: James D
authors.initials: JD
authors.lastname: Belluzzi
authors.forename: Frances M
authors.initials: FM
authors.lastname: Leslie
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000139:chemically induced* / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity*; D009538:Nicotine / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D012701:Serotonin / Q000378:metabolism; D014191:Tranylcypromine / Q000633:toxicity*
chemical_list: D008996:Monoamine Oxidase Inhibitors; D012701:Serotonin; D014191:Tranylcypromine; D009538:Nicotine; D008995:Monoamine Oxidase; D004298:Dopamine