Koob George F
National Institute on Alcohol Abuse and Alcoholism, Washington, DC, USA.
Eur J Pharmacol. 2015 Apr 15;753:73-87. doi: 10.1016/j.ejphar.2014.11.044. Epub 2015 Jan 9.
Emotions are "feeling" states and classic physiological emotive responses that are interpreted based on the history of the organism and the context. Motivation is a persistent state that leads to organized activity. Both are intervening variables and intimately related and have neural representations in the brain. The present thesis is that drugs of abuse elicit powerful emotions that can be interwoven conceptually into this framework. Such emotions range from pronounced euphoria to a devastating negative emotional state that in the extreme can create a break with homeostasis and thus an allostatic hedonic state that has been considered key to the etiology and maintenance of the pathophysiology of addiction. Drug addiction can be defined as a three-stage cycle-binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation-that involves allostatic changes in the brain reward and stress systems. Two primary sources of reinforcement, positive and negative reinforcement, have been hypothesized to play a role in this allostatic process. The negative emotional state that drives negative reinforcement is hypothesized to derive from dysregulation of key neurochemical elements involved in the brain incentive salience and stress systems. Specific neurochemical elements in these structures include not only decreases in incentive salience system function in the ventral striatum (within-system opponent processes) but also recruitment of the brain stress systems mediated by corticotropin-releasing factor (CRF), dynorphin-κ opioid systems, and norepinephrine, vasopressin, hypocretin, and substance P in the extended amygdala (between-system opponent processes). Neuropeptide Y, a powerful anti-stress neurotransmitter, has a profile of action on compulsive-like responding for drugs similar to a CRF1 receptor antagonist. Other stress buffers include nociceptin and endocannabinoids, which may also work through interactions with the extended amygdala. The thesis argued here is that the brain has specific neurochemical neurocircuitry coded by the hedonic extremes of pleasant and unpleasant emotions that have been identified through the study of opponent processes in the domain of addiction. These neurochemical systems need to be considered in the context of the framework that emotions involve the specific brain regions now identified to differentially interpreting emotive physiological expression.
情绪是基于生物体的历史和情境进行解读的“感觉”状态及经典生理情感反应。动机是一种导致有组织活动的持续状态。二者均为中介变量，密切相关且在大脑中有神经表征。本论文的观点是，滥用药物会引发强烈情绪，这些情绪在概念上可融入此框架。此类情绪范围从明显的欣快感至极具破坏性的负面情绪状态，极端情况下会打破内稳态，进而形成一种被认为是成瘾病理生理学病因及维持的关键的异稳态享乐状态。药物成瘾可被定义为一个三阶段循环—— binge / 中毒、戒断 / 负面效应以及专注 / 期待—— 这涉及大脑奖赏和应激系统的异稳态变化。两种主要强化源，即正强化和负强化，被假定在这个异稳态过程中发挥作用。驱使负强化的负面情绪状态被假定源自大脑奖赏显著性和应激系统中关键神经化学元素的失调。这些结构中的特定神经化学元素不仅包括腹侧纹状体中奖赏显著性系统功能的降低（系统内对抗过程），还包括由促肾上腺皮质激素释放因子（CRF）、强啡肽 - κ阿片系统以及去甲肾上腺素、血管加压素、下丘脑泌素和P物质介导的大脑应激系统在杏仁核扩展区的激活（系统间对抗过程）。神经肽Y是一种强大的抗应激神经递质，其对药物强迫样反应的作用模式类似于CRF1受体拮抗剂。其他应激缓冲物质包括孤啡肽和内源性大麻素，它们也可能通过与杏仁核扩展区的相互作用发挥作用。此处所论证的观点是，大脑具有由愉悦和不愉快情绪的享乐极端所编码的特定神经化学神经回路，这些情绪已通过成瘾领域中对抗过程的研究得以确定。这些神经化学系统需要在这样一个框架背景下进行考量，即情绪涉及现已确定的不同地解读情感生理表达的特定脑区。
