Koob G F
Department of Neuropharmacology, CVN-7, Scripps Research Institute, La Jolla, California 92037, USA.
Ann N Y Acad Sci. 1999 Jun 29;877:445-60. doi: 10.1111/j.1749-6632.1999.tb09282.x.
Evidence suggests that the acute reinforcing actions of drugs of abuse may be mediated by specific elements of the striatopallidal and extended amygdala systems. These include the shell of the nucleus accumbens, the central nucleus of the amygdala, and the sublenticular extended amygdala. Chronic administration of drugs of abuse, including cocaine, amphetamines, nicotine, alcohol, and tetrahydrocannabinol leads to an increasing dysregulation of brain reward systems that is characterized by decreases in reward function. Withdrawal from chronic administration of cocaine, amphetamine, nicotine, alcohol, and tetrahydrocannabinol raises thresholds for brain stimulation reward. Neurochemical elements in the extended amygdala may mediate these changes, including decreases in dopamine and serotonin neurotransmission in the nucleus accumbens and increases in the brain-stress neurotransmitter, corticotropin-releasing factor, in the central nucleus of the amygdala. The combination of decreases in function of neurotransmitters involved in the positive-reinforcing properties of drugs of abuse with recruitment of brain-stress systems within the extended amygdala provides a powerful mechanism for allostatic changes in hedonic set point that can lead to the compulsive drug-seeking and drug-taking behavior characteristic of addiction.
有证据表明，滥用药物的急性强化作用可能由纹状体苍白球系统和扩展杏仁核系统的特定元件介导。这些元件包括伏隔核壳、杏仁核中央核和豆状核下扩展杏仁核。长期服用包括可卡因、苯丙胺、尼古丁、酒精和四氢大麻酚在内的滥用药物会导致大脑奖赏系统的失调加剧，其特征是奖赏功能下降。长期服用可卡因、苯丙胺、尼古丁、酒精和四氢大麻酚后停药会提高大脑刺激奖赏的阈值。扩展杏仁核中的神经化学元件可能介导这些变化，包括伏隔核中多巴胺和5-羟色胺神经传递的减少，以及杏仁核中央核中脑应激神经递质促肾上腺皮质激素释放因子的增加。参与滥用药物正性强化特性的神经递质功能下降，与扩展杏仁核内脑应激系统的激活相结合，为享乐设定点的适应性变化提供了一个强大的机制，这可能导致成瘾所特有的强迫性觅药和用药行为。
