Jentsch J D, Taylor J R
Section of Neurobiology, Yale University School of Medicine, 333 Cedar Street, P.O. Box 208001, New Haven, CT 06520-8001, USA.
Psychopharmacology (Berl). 1999 Oct;146(4):373-90. doi: 10.1007/pl00005483.
Drug abuse and dependence define behavioral states involving increased allocation of behavior towards drug seeking and taking at the expense of more appropriate behavioral patterns. As such, addiction can be viewed as increased control of behavior by the desired drug (due to its unconditioned, rewarding properties). It is also clear that drug-associated (conditioned) stimuli acquire heightened abilities to control behaviors. These phenomena have been linked with dopamine function within the ventral striatum and amygdala and have been described specifically in terms of motivational and incentive learning processes. New data are emerging that suggest that regions of the frontal cortex involved in inhibitory response control are directly affected by long-term exposure to drugs of abuse. The result of chronic drug use may be frontal cortical cognitive dysfunction, resulting in an inability to inhibit inappropriate unconditioned or conditioned responses elicited by drugs, by related stimuli or by internal drive states. Drug-seeking behavior may thus be due to two related phenomena: (1) augmented incentive motivational qualities of the drug and associated stimuli (due to limbic/amygdalar dysfunction) and (2) impaired inhibitory control (due to frontal cortical dysfunction). In this review, we consider the neuro-anatomical and neurochemical substrates subserving inhibitory control and motivational processes in the rodent and primate brain and their putative impact on drug seeking. The evidence for cognitive impulsivity in drug abuse associated with dysfunction of the frontostriatal system will be discussed, and an integrative hypothesis for compulsive reward-seeking in drug abuse will be presented.
药物滥用和药物依赖定义了一些行为状态，这些状态涉及行为分配的增加，即更多地倾向于寻求和使用药物，而牺牲了更合适的行为模式。因此，成瘾可被视为所需药物对行为的控制增强（由于其无条件的奖励特性）。同样明显的是，与药物相关的（条件性）刺激获得了更强的控制行为的能力。这些现象与腹侧纹状体和杏仁核内的多巴胺功能有关，并已具体根据动机和激励学习过程进行了描述。新出现的数据表明，参与抑制性反应控制的额叶皮质区域会受到长期滥用药物的直接影响。长期使用药物的结果可能是额叶皮质认知功能障碍，导致无法抑制由药物、相关刺激或内部驱动状态引发的不适当的无条件或条件性反应。因此，寻求药物的行为可能归因于两个相关现象：（1）药物和相关刺激的激励动机特性增强（由于边缘系统/杏仁核功能障碍）以及（2）抑制控制受损（由于额叶皮质功能障碍）。在本综述中，我们考虑了在啮齿动物和灵长类动物大脑中支持抑制控制和动机过程的神经解剖学和神经化学基础，以及它们对药物寻求的假定影响。我们将讨论与额纹状体系统功能障碍相关的药物滥用中认知冲动性的证据，并提出一个关于药物滥用中强迫性寻求奖励的综合假设。
