Kreek Mary Jeanne, Zhou Yan, Butelman Eduardo R, Levran Orna
The Rockefeller University, Laboratory of the Biology of Addictive Diseases, 1230 York Avenue, Box 171, New York, NY 10065, United States.
Curr Opin Pharmacol. 2009 Feb;9(1):74-80. doi: 10.1016/j.coph.2008.12.016. Epub 2009 Jan 18.
This review primarily focuses on our recent findings in bidirectional translational research on opiate and cocaine addictions. First, we present neurobiological and molecular studies on endogenous opioid systems (e.g. proopiomelanocortin, mu opioid receptor, dynorphin, and kappa opioid receptor), brain stress-responsive systems (e.g. orexin, arginine vasopressin, V1b receptor, and corticotropin-releasing factor), hypothalamic-pituitary-adrenal axis, and neurotransmitters (especially dopamine), in response to both chronic cocaine or opiate exposure and to drug withdrawal, using several newly developed animal models and molecular approaches. The second aspect is human molecular genetic association investigations including hypothesis-driven studies and genome-wide array studies, to define particular systems involved in vulnerability to develop specific addictions, and response to pharmacotherapy.
本综述主要聚焦于我们近期在阿片类药物和可卡因成瘾双向转化研究中的发现。首先，我们介绍了对内源性阿片系统（如阿片促黑激素皮质素原、μ阿片受体、强啡肽和κ阿片受体）、脑应激反应系统（如食欲素、精氨酸加压素、V1b受体和促肾上腺皮质激素释放因子）、下丘脑-垂体-肾上腺轴以及神经递质（尤其是多巴胺）的神经生物学和分子研究，这些研究采用了几种新开发的动物模型和分子方法，以应对慢性可卡因或阿片类药物暴露以及药物戒断的情况。第二个方面是人类分子遗传关联研究，包括假设驱动研究和全基因组阵列研究，以确定参与特定成瘾易感性和药物治疗反应的特定系统。
