Ritz M C, Kuhar M J
Department of Psychiatry, University of New Mexico, Albuquerque 87131.
Biochem Soc Symp. 1993;59:51-64.
Evidence that psychostimulant drugs interact principally with monoamines, and in particular with the mesolimbic pathway that utilizes dopamine as the neurotransmitter, has prompted the dopamine hypothesis of psychostimulant addiction. This hypothesis proposes that enhancement of dopamine neurotransmission in the mesolimbic pathway is fundamental to the reinforcing properties of many drugs of abuse. Cocaine, the best characterized psychostimulant, is seen to fulfil this hypothesis by blocking dopamine transporters, thereby preventing re-uptake of the neurotransmitter and enhancing its synaptic concentration (Fig. 1). This biochemical mechanism is supported by behavioural data. For example, concordance between binding to the transporter and changes in locomotor activity has been demonstrated for a large series of cocaine analogues. The dopamine hypothesis suggests possible pharmacotherapeutic strategies to combat psychostimulant use, and these approaches, including available human data and future directions of pharmacological treatments are discussed in this paper. The limitations of the dopamine hypothesis with respect to psychostimulant dependence and abuse liability are also summarized, to provide a broad perspective of the current status of this hypothesis.
有证据表明，精神兴奋药物主要与单胺相互作用，特别是与以多巴胺作为神经递质的中脑边缘通路相互作用，这催生了精神兴奋药物成瘾的多巴胺假说。该假说提出，中脑边缘通路中多巴胺神经传递的增强对于许多滥用药物的强化特性至关重要。可卡因是特征最明确的精神兴奋药物，它通过阻断多巴胺转运体来满足这一假说，从而阻止神经递质的再摄取并提高其突触浓度（图1）。这一生物化学机制得到了行为数据的支持。例如，对于一系列可卡因类似物，已证明其与转运体的结合和运动活动变化之间存在一致性。多巴胺假说提出了对抗精神兴奋药物使用的可能药物治疗策略，本文将讨论这些方法，包括现有的人体数据和药物治疗的未来方向。本文还总结了多巴胺假说在精神兴奋药物依赖和滥用倾向方面的局限性，以提供对该假说当前状况的广泛视角。
