Monoamine oxidase inhibition dramatically increases the motivation to self-administer nicotine in rats.
Nicotine is the major neuroactive compound of tobacco, which has, by itself, weak reinforcing properties. It is known that levels of the enzymes monoamine oxidase A (MAO-A) and MAO-B are reduced in the platelets and brains of smokers and that substances, other than nicotine, present in tobacco smoke have MAO-inhibitory activities. Here, we report that inhibition of MAO dramatically and specifically increases the motivation to self-administer nicotine in rats. These effects were more prominent in rats selected for high responsiveness to novelty than in rats with low responsiveness to novelty. The results suggest that the inhibition of MAO activity by compounds present in tobacco smoke may combine with nicotine to produce the intense reinforcing properties of cigarette smoking that lead to addiction.
Guillem
Karine
K
Laboratoire de Neuropsychobiologie des Désadaptations, Unité Mixte de Recherche 5541, Centre National de la Recherche Scientifique, Université de Bordeaux 2, 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
D000818:Animals; D016739:Behavior, Addictive / Q000201:enzymology*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009042:Motivation; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration
D008996:Monoamine Oxidase Inhibitors; D009538:Nicotine; D008995:Monoamine Oxidase