Di Chiara Gaetano, Bassareo Valentina
Department of Toxicology, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy.
Curr Opin Pharmacol. 2007 Feb;7(1):69-76. doi: 10.1016/j.coph.2006.11.003. Epub 2006 Dec 15.
Addictive drugs share with palatable food the property of increasing extracellular dopamine (DA), preferentially in the nucleus accumbens shell rather than in the core. However, by acting directly on the brain, drugs bypass the adaptive mechanisms (habituation) that constrain the responsiveness of accumbens shell DA to food reward, abnormally facilitating Pavlovian incentive learning and promoting the acquisition of abnormal DA-releasing properties by drug conditioned stimuli. Thus, whereas Pavlovian food conditioned stimuli release core but not shell DA, drug conditioned stimuli do the opposite, releasing shell but not core DA. This process, which results in the acquisition of excessive incentive-motivational properties by drug conditioned stimuli, initiates the drug addiction process. Neuroadaptive processes related to the chronic influence of drugs on subcortical DA might secondarily impair the function of prefronto-striatal loops, resulting in impairments in impulse control and decision making that form the basis for the compulsive feature of drug seeking and its relapsing character.
成瘾性药物与美味食物具有共同特性，即优先增加伏隔核壳而非核心区域的细胞外多巴胺（DA）。然而，药物通过直接作用于大脑，绕过了限制伏隔核壳DA对食物奖励反应性的适应性机制（习惯化），异常地促进了巴甫洛夫式动机学习，并通过药物条件刺激促进了异常DA释放特性的习得。因此，巴甫洛夫式食物条件刺激释放核心区域而非壳区域的DA，而药物条件刺激则相反，释放壳区域而非核心区域的DA。这一过程导致药物条件刺激获得过度的动机激励特性，从而启动药物成瘾过程。与药物对皮质下DA的慢性影响相关的神经适应性过程可能继而损害前额叶-纹状体环路的功能，导致冲动控制和决策受损，而这构成了药物寻求的强迫性特征及其复发性的基础。
