Blum K, Braverman E R, Holder J M, Lubar J F, Monastra V J, Miller D, Lubar J O, Chen T J, Comings D E
Department of Biological Sciences, University of North Texas, Denton, Texas, USA.
J Psychoactive Drugs. 2000 Nov;32 Suppl:i-iv, 1-112. doi: 10.1080/02791072.2000.10736099.
The dopaminergic system, and in particular the dopamine D2 receptor, has been implicated in reward mechanisms. The net effect of neurotransmitter interaction at the mesolimbic brain region induces "reward" when dopamine (DA) is released from the neuron at the nucleus accumbens and interacts with a dopamine D2 receptor. "The reward cascade" involves the release of serotonin, which in turn at the hypothalmus stimulates enkephalin, which in turn inhibits GABA at the substania nigra, which in turn fine tunes the amount of DA released at the nucleus accumbens or "reward site." It is well known that under normal conditions in the reward site DA works to maintain our normal drives. In fact, DA has become to be known as the "pleasure molecule" and/or the "antistress molecule." When DA is released into the synapse, it stimulates a number a DA receptors (D1-D5) which results in increased feelings of well-being and stress reduction. A consensus of the literature suggests that when there is a dysfunction in the brain reward cascade, which could be caused by certain genetic variants (polygenic), especially in the DA system causing a hypodopaminergic trait, the brain of that person requires a DA fix to feel good. This trait leads to multiple drug-seeking behavior. This is so because alcohol, cocaine, heroin, marijuana, nicotine, and glucose all cause activation and neuronal release of brain DA, which could heal the abnormal cravings. Certainly after ten years of study we could say with confidence that carriers of the DAD2 receptor A1 allele have compromised D2 receptors. Therefore lack of D2 receptors causes individuals to have a high risk for multiple addictive, impulsive and compulsive behavioral propensities, such as severe alcoholism, cocaine, heroin, marijuana and nicotine use, glucose bingeing, pathological gambling, sex addiction, ADHD, Tourette's Syndrome, autism, chronic violence, posttraumatic stress disorder, schizoid/avoidant cluster, conduct disorder and antisocial behavior. In order to explain the breakdown of the reward cascade due to both multiple genes and environmental stimuli (pleiotropism) and resultant aberrant behaviors, Blum united this hypodopaminergic trait under the rubric of a reward deficiency syndrome.
多巴胺能系统，尤其是多巴胺D2受体，与奖赏机制有关。当中脑边缘脑区的神经递质相互作用的净效应导致多巴胺（DA）从伏隔核的神经元释放并与多巴胺D2受体相互作用时，就会诱发“奖赏”。“奖赏级联反应”涉及血清素的释放，血清素继而在下丘脑刺激脑啡肽，脑啡肽继而在黑质抑制γ-氨基丁酸（GABA），γ-氨基丁酸继而微调在伏隔核或“奖赏位点”释放的多巴胺量。众所周知，在正常情况下，奖赏位点的多巴胺作用是维持我们的正常驱动力。事实上，多巴胺已被称为“愉悦分子”和/或“抗应激分子”。当多巴胺释放到突触中时，它会刺激多种多巴胺受体（D1 - D5），从而增强幸福感并减轻压力。文献的共识表明，当大脑奖赏级联反应出现功能障碍时，这可能由某些基因变异（多基因）引起，尤其是在多巴胺系统中导致多巴胺能不足的特征，那么这个人的大脑就需要补充多巴胺才能感觉良好。这种特征会导致多种寻求药物的行为。之所以如此，是因为酒精、可卡因、海洛因、大麻、尼古丁和葡萄糖都会导致大脑多巴胺的激活和神经元释放，这可以缓解异常的渴望。当然，经过十年的研究，我们可以自信地说，携带多巴胺D2受体A1等位基因的个体其D2受体受损。因此，缺乏D2受体导致个体具有多种成瘾、冲动和强迫行为倾向的高风险，如严重酗酒、使用可卡因、海洛因、大麻和尼古丁、暴饮暴食、病态赌博、性成瘾、注意力缺陷多动障碍（ADHD）、妥瑞氏症、自闭症、慢性暴力、创伤后应激障碍、分裂样/回避型人格、品行障碍和反社会行为。为了解释由于多种基因和环境刺激（多效性）导致的奖赏级联反应中断以及由此产生的异常行为，布卢姆将这种多巴胺能不足的特征归为奖赏缺乏综合征。
