title: Monoamine oxidase inhibitors allow locomotor and rewarding responses to nicotine.
abstract: Although nicotine is generally considered to be the main compound responsible for the addictive properties of tobacco, experimental data indicate that nicotine does not exhibit all the characteristics of other abused substances, such as psychostimulants and opiates. For example, nicotine is only a weak locomotor enhancer in rats and generally fails to induce a locomotor response in mice. This observation contradicts the general consensus that all drugs of abuse release dopamine in the nucleus accumbens, a subcortical structure, and thus increase locomotor activity in rodents. Because tobacco smoke contains monoamine oxidase inhibitors (MAOIs) and decreases MAO activity in smokers, we have combined MAOIs with nicotine to determine whether it is possible to obtain a locomotor response to nicotine in C57Bl6 mice. Among 15 individual or combined MAOIs, including harmane, norharmane, moclobemide, selegiline, pargyline, clorgyline, tranylcypromine and phenelzine, only irreversible inhibitors of both MAO-A and -B (tranylcypromine, phenelzine, and clorgyline+selegiline) allowed a locomotor response to nicotine. The locomotor stimulant interaction of tranylcypromine and nicotine was absent in beta2-nicotinic acetylcholine receptor subunit knockout mice. Finally, it was found that, whereas naïve rats did not readily self-administer nicotine (10 microg/kg/injection), a robust self-administration of nicotine occurred when animals were pretreated with tranylcypromine (3 mg/kg). Our data suggest that MAOIs contained in tobacco and tobacco smoke act in synergy with nicotine to enhance its rewarding effects.
authors.affiliation: Inserm U.114, Collège de France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Villégier
authors.forename: Lucas
authors.initials: L
authors.lastname: Salomon
authors.forename: Sylvie
authors.initials: S
authors.lastname: Granon
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Changeux
authors.forename: James D
authors.initials: JD
authors.lastname: Belluzzi
authors.forename: Frances M
authors.initials: FM
authors.lastname: Leslie
authors.forename: Jean-Pol
authors.initials: JP
authors.lastname: Tassin
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000172:deficiency / Q000502:physiology; D012201:Reward; D012646:Self Administration
chemical_list: D008996:Monoamine Oxidase Inhibitors; D011978:Receptors, Nicotinic; D009538:Nicotine