Monoamine oxidase A rather than monoamine oxidase B inhibition increases nicotine reinforcement in rats

Eur J Neurosci. 2006 Dec;24(12):3532-40. doi: 10.1111/j.1460-9568.2006.05217.x.


Although nicotine is considered to be responsible for the addictive properties of tobacco, growing evidence underlines the importance of non-nicotine components in smoking reinforcement. It has been shown that tobacco smoke contains monoamine oxidase (MAO) A and B inhibitors and decreases MAO-A and MAO-B activity in smokers. Here, we investigated the effects of clorgyline hydrochloride (irreversible MAO-A inhibitor; 2 mg/kg/day), selegiline (irreversible MAO-B inhibitor; 4 mg/kg) and the beta-carboline norharmane hydrochloride (reversible MAO-B inhibitor; 5 mg/kg/day) treatments on nicotine self-administration (30 microg/kg/infusion, free base) in rats. Independent of the responsiveness to novelty and locomotor activity stimulation, only clorgyline hydrochloride treatment increased the intake of nicotine in a fixed-ratio schedule (FR5) of reinforcement. When a progressive-ratio schedule was implemented, both clorgyline hydrochloride and norharmane hydrochloride treatments potentiated the reinforcing effects of nicotine, whereas selegiline had no effect. Taken together, these results indicate that MAO-A inhibition interacts with nicotine to enhance its rewarding effects in rats and suggest that other compounds present in tobacco, such as beta-carboline, may also play an important role in sustaining smoking behavior in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects
  • Cotinine / blood
  • Drug Interactions
  • Male
  • Monoamine Oxidase / physiology*
  • Monoamine Oxidase Inhibitors / blood
  • Monoamine Oxidase Inhibitors / pharmacology
  • Motor Activity / drug effects
  • Nicotine / administration & dosage*
  • Nicotine / blood
  • Nicotinic Agonists / administration & dosage*
  • Nicotinic Agonists / blood
  • Rats
  • Rats, Wistar
  • Reinforcement Schedule
  • Reinforcement, Psychology*
  • Self Administration / methods
  • Time Factors


  • Monoamine Oxidase Inhibitors
  • Nicotinic Agonists
  • Nicotine
  • Monoamine Oxidase
  • Cotinine