Irreversible blockade of monoamine oxidases reveals the critical role of 5-HT transmission in locomotor response induced by nicotine in mice

Eur J Neurosci. 2006 Sep;24(5):1359-65. doi: 10.1111/j.1460-9568.2006.05011.x. Epub 2006 Sep 8.


Although nicotine is generally considered as the main compound responsible for addictive properties of tobacco, some experimental data indicate that nicotine does not exhibit all the characteristics of other substances of misuse such as psychostimulants and opiates. For example, nicotine generally fails to induce locomotor response in mice and self-administration of nicotine is difficult to obtain in rats. We have shown recently that a pretreatment with mixed irreversible monoamine oxidase inhibitors (MAOIs), such as tranylcypromine, triggers a locomotor response to nicotine in mice and induces a robust self-administration of nicotine in rats. We show here that when mice were pretreated with enhancers of extracellular levels of noradrenaline, dopamine or serotonin (D-amphetamine, GBR12783 or para-chloro-amphetamine, respectively) and injected with nicotine (1 mg/kg), only those animals pretreated with para-chloro-amphetamine exhibited a specific locomotor response to nicotine. These data indicate a critical role of serotonin in nicotine-induced locomotor activity in mice. This was further confirmed in microdialysis experiments showing that nicotine induces an increase in extracellular serotonin levels in the ventral striatum in mice pretreated with tranylcypromine. This effect of nicotine on extracellular serotonin levels was absent in mice lacking the beta2-subunit of the nicotinic acetylcholine receptor. Our data suggest that mixed irreversible MAOIs contained in tobacco facilitate the effects of nicotine on serotonin release, thus allowing the locomotor and rewarding effects of nicotine.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Brain Chemistry / drug effects
  • Drug Interactions
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Microdialysis / methods
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors / pharmacology
  • Motor Activity / drug effects*
  • Nicotine / pharmacology*
  • Nicotinic Agonists / pharmacology*
  • Receptors, Nicotinic / deficiency
  • Serotonin / physiology*
  • Serotonin Agents / pharmacology
  • Time Factors
  • Tranylcypromine / pharmacology
  • p-Chloroamphetamine / pharmacology


  • Monoamine Oxidase Inhibitors
  • Nicotinic Agonists
  • Receptors, Nicotinic
  • Serotonin Agents
  • nicotinic receptor beta2
  • Serotonin
  • Tranylcypromine
  • p-Chloroamphetamine
  • Nicotine
  • Monoamine Oxidase