The neural basis of addiction: A pathology of motivation and choice
The neural basis of addiction: A pathology of motivation and choice
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DOI：
10.1176/appi.ajp.162.8.1403
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发表时间：
2005-08-01
影响因子：
17.7
通讯作者：
Volkow, ND
中科院分区：
文献类型：
--
作者：
Kalivas, PW;Volkow, ND
目的：药物成瘾的一个主要的行为病理是动机强度过强，控制毒品欲望的能力下降。在这篇综述中，作者探索了神经生物学的进展如何接近于对成瘾的细胞和电路基础的理解，并描述了由此产生的新的药物治疗靶点。方法：成瘾者的神经成像结果与药物寻找的动物模型的细胞研究相结合。结果：尽管多巴胺对急性奖赏和成瘾的启动至关重要，但终末期成瘾主要是由于前扣带回和眶前额谷氨酸能投射到伏核的细胞适应。兴奋性传递中的病理生理可塑性降低了前额叶皮质对生物奖励发起行为的能力，并提供了对药物寻找的执行控制。同时，前额叶皮质对预测药物可获得性的刺激反应强烈，导致伏核内兴奋性突触调节神经传递能力降低的超生理谷氨酸驱动。结论：伏隔核前额叶谷氨酸能神经支配的细胞适应通过降低自然奖赏的价值，减少认知控制(选择)，增强对药物相关刺激的谷氨酸驱动，促进成瘾者寻求毒品的强迫特征。
Objective: A primary behavioral pathology in drug addiction is the overpowering motivational strength and decreased ability to control the desire to obtain drugs. In this review the authors explore how advances in neurobiology are approaching an understanding of the cellular and circuitry underpinnings of addiction, and they describe the novel pharmacotherapeutic targets emerging from this understanding.Method: Findings from neuroimaging of addicts are integrated with cellular studies in animal models of drug seeking.Results: While dopamine is critical for acute reward and initiation of addiction, end-stage addiction results primarily from cellular adaptations in anterior cingulate and orbitofrontal glutamatergic projections to the nucleus accumbens. Pathophysiological plasticity in excitatory transmission reduces the capacity of the prefrontal cortex to initiate behaviors in response to biological rewards and to provide executive control over drug seeking. Simultaneously, the prefrontal cortex is hyperresponsive to stimuli predicting drug availability, resulting in supraphysiological glutamatergic drive in the nucleus accumbens, where excitatory synapses have a reduced capacity to regulate neurotransmission.Conclusions: Cellular adaptations in prefrontal glutamatergic innervation of the accumbens promote the compulsive character of drug seeking in addicts by decreasing the value of natural rewards, diminishing cognitive control ( choice), and enhancing glutamatergic drive in response to drug-associated stimuli.