Monoamine oxidase inhibition dramatically prolongs the duration of nicotine withdrawal-induced place aversion.
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.
Guillem
Karine
K
Laboratoire de Neuropsychobiologie des Désadaptations UMR CNRS 5541, Université de Bordeaux 2, Bordeaux, France. guillemk@sas.upenn.edu
Vouillac
Caroline
C
Koob
George F
GF
Cador
Martine
M
Stinus
Luis
L
D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004347:Drug Interactions; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009538:Nicotine / Q000009:adverse effects; D018722:Nicotinic Agonists / Q000009:adverse effects; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000503:physiopathology / Q000523:psychology*
D008996:Monoamine Oxidase Inhibitors; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D008464:Mecamylamine; D009538:Nicotine; D008995:Monoamine Oxidase