Tranylcypromine enhancement of nicotine self-administration

Neuropharmacology. 2007 May;52(6):1415-25. doi: 10.1016/j.neuropharm.2007.02.001. Epub 2007 Feb 20.


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.

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Aging / physiology
  • Animals
  • Benzazepines / pharmacology
  • Chromatography, High Pressure Liquid
  • Cocaine / pharmacology
  • Dopamine / metabolism
  • Dopamine Antagonists / pharmacology
  • Dopamine Uptake Inhibitors / pharmacology
  • Dose-Response Relationship, Drug
  • Electrochemistry
  • Half-Life
  • Male
  • Microdialysis
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Nicotine / pharmacology*
  • Nicotinic Agonists / pharmacology*
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Reward
  • Self Administration
  • Tranylcypromine / pharmacology*


  • Benzazepines
  • Dopamine Antagonists
  • Dopamine Uptake Inhibitors
  • Monoamine Oxidase Inhibitors
  • Nicotinic Agonists
  • Receptors, Dopamine D1
  • 3,4-Dihydroxyphenylacetic Acid
  • Tranylcypromine
  • Nicotine
  • Cocaine
  • Dopamine