Title : Tranylcypromine enhancement of nicotine self-administration - Villegier_2007_Neuropharmacol_52_1415
Author(s) : Villegier AS , Lotfipour S , McQuown SC , Belluzzi JD , Leslie FM
Ref : Neuropharmacology , 52 :1415 , 2007
Abstract :

Tobacco use has one of the highest rates of addiction of any abused drug. Paradoxically, in animal models, nicotine appears to be a weak reinforcer. We report here that the inhibition of monoamine oxidase (MAO), a major effect of tobacco smoke, increases the reinforcing effect of nicotine. Rats (aged postnatal day 27 and 90) were tested for self-administration, without prior response training, in five daily 3-h sessions. Whereas control rats did not self-administer nicotine, low doses of nicotine (2.5 to 21 microg/kg/injection) were avidly self-administered following a pretreatment with tranylcypromine (3 mg/kg), an irreversible and non-selective MAO inhibitor. Tranylcypromine-enhanced nicotine (10 microg/kg/injection, i.v.) self-administration was reduced by systemic injection of a D1-dopaminergic receptor antagonist, SCH23390 (0.02 mg/kg). Moreover, an increase in extracellular dopamine in the nucleus accumbens was detected, using microdialysis, following nicotine (60 microg/kg) injection in tranylcypromine pre-treated rats. Depending on the time of tranylcypromine pretreatment (20 or 1 h), MAO activity was decreased by 72% and 99% and nicotine intake at day 5 was increased by 619 and 997%, respectively. Taken together, these results indicate that in a stringent self-administration acquisition test, MAO inhibition increases the rewarding effect of low doses of nicotine, possibly via a dopamine-dependent mechanism.

PubMedSearch : Villegier_2007_Neuropharmacol_52_1415
PubMedID: 17412372

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Citations formats

Villegier AS, Lotfipour S, McQuown SC, Belluzzi JD, Leslie FM (2007)
Tranylcypromine enhancement of nicotine self-administration
Neuropharmacology 52 :1415

Villegier AS, Lotfipour S, McQuown SC, Belluzzi JD, Leslie FM (2007)
Neuropharmacology 52 :1415