Center for Neurobiology of Stress, Department of Psychology, University of Toronto Scarborough, Toronto, Ontario, Canada M1C 1A4.
Prog Neuropsychopharmacol Biol Psychiatry. 2010 Jun 30;34(5):798-807. doi: 10.1016/j.pnpbp.2009.11.025. Epub 2009 Dec 5.
The initial termination of cocaine consumption in human addicts is associated with heightened anxiety states and low levels of craving. Craving, however, tends to increase progressively over time, remains high for extended periods of time, and can be exacerbated by stressors, leading to relapse. Laboratory rats, likewise, exhibit heightened states of anxiety after withdrawal from drug, and follow a time course of cocaine seeking that parallels the time course of craving reported in humans. In addition, laboratory rats show heightened susceptibility to relapse when exposed to stressors after extended periods of withdrawal, and exhibit persistent and heightened expressions of stress-induced anxiety. The general objective of this paper is to consider the relationship between anxiety states after withdrawal from cocaine and stress-induced reinstatement of cocaine seeking in laboratory rats, and to identify the neural substrates involved. The focus of the review is on studies addressing the roles of corticotropin-releasing factor (CRF) and noradrenaline pathways of the extended amygdala circuitry, and their direct or indirect interactions with the mesocorticolimbic dopamine system, in anxiety after withdrawal from cocaine and stress-induced reinstatement of cocaine seeking. Furthermore, the effects of time after withdrawal from cocaine and amount of cocaine exposure during self-administration on the activity of CRF, noradrenaline, and dopamine pathways of the extended amygdala and mesocorticolimbic systems will be considered. The review will highlight how changing levels of activity within these systems may serve to alter the nature of the relationship between anxiety and stress-induced reinstatement of cocaine seeking at different times after withdrawal from cocaine.
人类成瘾者停止可卡因消费最初与焦虑状态加剧和渴望程度降低有关。然而，渴望往往会随着时间的推移逐渐增加，持续时间长，并可能因应激源而加剧，导致复发。同样，实验室大鼠在戒除毒品后也会表现出高度的焦虑状态，并遵循与人类报告的渴望时间过程相似的可卡因寻求时间过程。此外，实验室大鼠在长时间戒断后暴露于应激源时，复发的易感性增加，并表现出持续和高度的应激诱导焦虑表达。本文的总体目标是考虑可卡因戒断后焦虑状态与实验室大鼠应激诱导可卡因寻求复燃之间的关系，并确定涉及的神经基质。综述的重点是研究皮质激素释放因子（CRF）和延伸杏仁核电路的去甲肾上腺素途径的作用，以及它们与中脑边缘多巴胺系统的直接或间接相互作用，在可卡因戒断后的焦虑和应激诱导的可卡因寻求复燃中的作用。此外，还将考虑从可卡因戒断后的时间和自我给药期间可卡因暴露量对延伸杏仁核和中脑边缘多巴胺系统的 CRF、去甲肾上腺素和多巴胺途径活性的影响。该综述将强调这些系统内活动水平的变化如何可能改变焦虑和应激诱导可卡因寻求复燃之间关系的性质，这取决于从可卡因戒断后的不同时间。
