Wooters Thomas E, Bevins Rick A, Bardo Michael T
Department of Psychology, BBSRB, University of Kentucky, Lexington, KY 40536-0509, USA.
Curr Drug Abuse Rev. 2009 Sep;2(3):243-55. doi: 10.2174/1874473710902030243.
Preclinical drug discrimination techniques play a significant role in advancing our knowledge of the receptor mechanisms underlying the interoceptive effects of nicotine. Early reports confirmed that nicotinic acetylcholine receptors (nAChRs) are critical for transduction of the nicotine cue. In recent years, advances in molecular biology and the discovery of novel ligands with greater selectively for specific nAChR subtypes have furthered our understanding of these mechanisms. There is now evidence regarding the specific nAChR subtypes involved in nicotine discrimination; in addition, there is also evidence suggesting that other systems (i.e., adenosine, cannabinoid, dopamine, glutamate and serotonin) may play a modulatory role. The neuroanatomical structures mediating the nicotine cue have also begun to be elucidated. However, much remains to be learned about the predictive validity of the drug discrimination procedure, particularly with regard to the relation between interoceptive and reinforcing effects and individual differences in vulnerability to tobacco dependence. Recent data also suggests that the mechanisms involved in the conditional and discriminative stimulus properties of nicotine may be dissociable. Avenues for future research should include assessing the mechanisms of the subjective effects of nicotine withdrawal, factors contributing to individual differences in sensitivity to the nicotine cue, and the role of behavioral factors involved in drug cross-substitution.
临床前药物辨别技术在推进我们对尼古丁内感受效应潜在受体机制的认识方面发挥着重要作用。早期报告证实，烟碱型乙酰胆碱受体（nAChRs）对于尼古丁信号的转导至关重要。近年来，分子生物学的进展以及对特定nAChR亚型具有更高选择性的新型配体的发现，进一步加深了我们对这些机制的理解。现在有证据表明哪些特定的nAChR亚型参与了尼古丁辨别；此外，也有证据表明其他系统（即腺苷、大麻素、多巴胺、谷氨酸和5-羟色胺）可能发挥调节作用。介导尼古丁信号的神经解剖结构也已开始得到阐明。然而，关于药物辨别程序的预测效度，尤其是关于内感受与强化效应之间的关系以及对烟草依赖易感性的个体差异，仍有许多需要了解的地方。最近的数据还表明，尼古丁的条件性和辨别性刺激特性所涉及的机制可能是可分离的。未来的研究途径应包括评估尼古丁戒断主观效应的机制、导致对尼古丁信号敏感性个体差异的因素，以及行为因素在药物交叉替代中的作用。
