Monoamine oxidase A rather than monoamine oxidase B inhibition increases nicotine reinforcement in rats.
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.
Guillem
Karine
K
Laboratoire de Neuropsychobiologie des Désadaptations, UMR CNRS 5541, Université de Bordeaux 2, BP 31, 146 rue Léo Saignat, 33076 Bordeaux, cedex, France.
Vouillac
Caroline
C
Azar
Marc R
MR
Parsons
Loren H
LH
Koob
George F
GF
Cador
Martine
M
Stinus
Luis
L
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003367:Cotinine / Q000097:blood; D004347:Drug Interactions; D008297:Male; D008995:Monoamine Oxidase / Q000502:physiology*; D008996:Monoamine Oxidase Inhibitors / Q000097:blood / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000008:administration & dosage* / Q000097:blood; D018722:Nicotinic Agonists / Q000008:administration & dosage* / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration / Q000379:methods; D013997:Time Factors
D008996:Monoamine Oxidase Inhibitors; D018722:Nicotinic Agonists; D009538:Nicotine; D008995:Monoamine Oxidase; D003367:Cotinine