Monoamine oxidase inhibition dramatically prolongs the duration of nicotine withdrawal-induced place aversion.
Biological Psychiatry. 2008-01-01; 63(2): 158-163
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Guillem K(1), Vouillac C, Koob GF, Cador M, Stinus L.
(1)Laboratoire de Neuropsychobiologie des Désadaptations UMR CNRS 5541,
Université de Bordeaux 2, Bordeaux, France.
BACKGROUND: Long-lasting effects of withdrawal from nicotine are hypothesized to
contribute to relapse and persistence of tobacco habits, and significant evidence
supports a role of monoamine oxidase inhibitors (MAOI) contained in cigarette
smoke as potent modulators of the rewarding effects of tobacco.
METHODS: With quantification of somatic signs of withdrawal and the place
aversion conditioning paradigm, we assessed the effects of MAOI pretreatment on
both somatic and aversive motivational components of mecamylamine-induced
nicotine withdrawal in rats rendered dependent on nicotine by the subcutaneous
implantation of osmotic minipumps (vehicle or nicotine tartrate 9 mg/kg/day).
RESULTS: In nicotine-infused rats, mecamylamine induced a place aversion that
lasted 6 weeks. When nicotine-infused rats were also treated with a MAOI,
mecamylamine-induced conditioned place aversion persisted for at least 8 months
of abstinence. The MAOI treatment slightly decreased ratings of somatic signs
induced by mecamylamine administration but had no effect on the threshold or the
magnitude of mecamylamine-induced conditioned place aversion.
CONCLUSIONS: These results show that MAOI pretreatment induces a long-lasting
conditioned placed aversion associated with nicotine withdrawal, possibly through
a potentiation of learning and memory process, and provides some indications on
protracted abstinence that might be useful for delineating the neurobiological
substrate of relapse.