Laviolette S R, van der Kooy D
Neurobiology Research Group, Department of Anatomy & Cell Biology, University of Toronto, Canada.
Mol Psychiatry. 2003 Jan;8(1):50-9, 9. doi: 10.1038/sj.mp.4001197.
Nicotine produces rewarding and aversive motivational effects in humans and other animal species. Here, we 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. We 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. Our 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.
尼古丁在人类和其他动物物种中会产生奖赏性和厌恶性动机效应。在此，我们报告称，哺乳动物腹侧被盖区（VTA）是介导尼古丁奖赏性和厌恶性特性的关键神经基础。我们证明，将尼古丁直接注入VTA可产生奖赏性和厌恶性动机效应。虽然高剂量尼古丁的奖赏效应不会因多巴胺（DA）受体阻断而减弱，但全身或伏隔核（NAc）内注射抗精神病药物预处理阻断中脑边缘DA信号，会在三个数量级的剂量范围内增强对尼古丁奖赏特性的敏感性。此外，较低剂量的VTA内尼古丁的行为效应会发生逆转，将尼古丁的动机效价从厌恶性转变为奖赏性。我们的结果表明，抗精神病药物诱导的中脑边缘DA信号阻断可能会选择性地阻断尼古丁的厌恶性特性，从而通过诱导一种独特的、药物易感性表型，增加对尼古丁奖赏性和成瘾性特性的易感性。
