Transient behavioral sensitization to nicotine becomes long-lasting with monoamine oxidases inhibitors.
Drugs of abuse, such as D-amphetamine or nicotine, are generally considered as acting through an increased release of dopamine in a subcortical structure, the nucleus accumbens, thus inducing locomotor hyperactivity in rats. Following repeated treatments, the same drugs induce a progressive increase in locomotor response called behavioral sensitization. This process has been suggested to play a role in the acquisition and maintenance of addictive behaviors. Here we show that whereas behavioral sensitization to D-amphetamine (0.5 and 0.75 mg/kg) stays constant following three consecutive periods of withdrawal (15, 30 and 30 days), the same experimental conditions completely abolish behavioral sensitization to 0.3 and 0.5 mg/kg nicotine. Indeed, following these periods of withdrawal, locomotor responses to nicotine are identical to those obtained at the first nicotine injection or after repeated saline injections. However, when a monoamine oxidases inhibitor (MAOI), tranylcypromine (3 mg/kg) or pargyline (30 mg/kg), is co-injected with nicotine, behavioral sensitization is maintained despite submission of the animals to the same withdrawal experimental design. Since tobacco smoke is known to contain many compounds including MAOIs, our data suggest that addictive properties of tobacco may not be limited to nicotine. We propose that MAOIs potentiate effects of nicotine on monoamines release.
Inserm U.114, Collège de France, 11, Place Marcelin Berthelot, 75231 Paris cedex 05, France.
Anne-Sophie
AS
Villégier
Gérard
G
Blanc
Jacques
J
Glowinski
Jean-Pol
JP
Tassin
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D004347:Drug Interactions; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014191:Tranylcypromine / Q000494:pharmacology
D000697:Central Nervous System Stimulants; D008996:Monoamine Oxidase Inhibitors; D018722:Nicotinic Agonists; D014191:Tranylcypromine; D009538:Nicotine; D010293:Pargyline; D003913:Dextroamphetamine