S R Laviolette and D van der Kooy

Neurobiology Research Group, Department of Anatomy & Cell Biology, University of Toronto, Toronto, Canada

Correspondence to: SR Laviolette, Neurobiology Research Group, Department of Anatomy & Cell Biology, 1 King's College Circle, University of Toronto, Toronto, Canada M5S 1A8

Nicotine produces rewarding and aversive motivational effects in humans and other animal species. Here, the authors report that the mammalian ventral tegmental area (VTA) represents a critical neural substrate for the mediation of both the rewarding and aversive properties of nicotine. They demonstrate that direct infusions of nicotine into the VTA can produce both rewarding and aversive motivational effects. While the rewarding effects of higher doses of nicotine were not attenuated by dopamine (DA) receptor blockade, blockade of mesolimbic DA signalling with either systemic or intra-nucleus accumbens (NAc) neuroleptic pretreatment potentiated the sensitivity to nicotine's rewarding properties over a three-order-of-magnitude dose range. Furthermore, the behavioural effects of lower doses of intra-VTA nicotine were reversed, switching the motivational valence of nicotine from aversive to rewarding. These results suggest that blockade of mesolimbic DA signalling induced by neuroleptic medications may block selectively the aversive properties of nicotine, thus increasing the vulnerability to nicotine's rewarding and addictive properties by inducing a unique, drug-vulnerable phenotype.

Citation source: Molecular Psychiatry 2003 Volume 8, number 1, pages 50-59.

For further information on this work, please contact Dr. Steven R. Laviolette, Neurobiology Research Group, Department of Anatomy & Cell Biology, 1 King's College Circle, University of Toronto, Toronto,
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13-Feb-2003