Department of Psychiatry, and McKnight Brain Institute, University of Florida, College of Medicine, Gainesville, Florida, USA.
Curr Pharm Des. 2011;17(12):1158-67. doi: 10.2174/138161211795656819.
Neural circuits implicated in drug conditioning, craving and relapse overlap extensively with those involved in natural reward and reinforcement like food. Exposure to drug-related cues in human addicts results in drug craving and localized activation of central circuits that are known to mediate cue-induced reinstatement of drug-seeking behavior in animal models of relapse. Similar regional activation patterns occur in humans in response to cues associated with foods. Furthermore, drug- and food-related cues not only activate common neuroanatomical regions but also result in similar activity-regulated gene expression programs within these shared areas. Cues predictive of food availability are powerful modulators of appetite as well as food-seeking and ingestive behaviors. The upregulation of a number of early genes in unique patterns within corticostriatal, thalamic, and hypothalamic networks suggests that food cues are capable of powerfully altering neuronal processing in areas mediating the integration of emotion, cognition, arousal, and the regulation of energy balance. The dopaminergic, enkephalinergic, and fos gene expressions are important regulatory genetic pathways for food craving behaviors. An umbrella term to describe common genetic antecedents of multiple impulsive, compulsive and addictive behaviors is Reward Deficiency Syndrome (RDS). Individuals possessing a paucity of serotonergic and/or dopaminergic receptors and an increased rate of synaptic dopamine catabolism, due to high catabolic genotype of the COMT gene, are predisposed to self-medicating any substance or behavior that will activate dopamine release including alcohol, opiates, psychostimulants, nicotine, glucose, gambling, sex, and even excessive internet gaming, among others. Finally, utilizing the long term dopaminergic activation approach will ultimately lead to a common safe and effective modality to treat RDS behaviors including aberrant food and drug craving behaviors.
涉及药物条件作用、渴望和复发的神经回路与涉及自然奖励和强化的回路（如食物）有很大的重叠。在人类成瘾者中，暴露于与药物相关的线索会导致药物渴望和中枢回路的局部激活，这些回路已知在动物复发模型中介导线索诱导的觅药行为的恢复。在人类中，类似的区域激活模式会对与食物相关的线索做出反应。此外，药物和食物相关的线索不仅激活共同的神经解剖区域，而且在这些共享区域内导致类似的活性调节基因表达程序。预测食物可获得性的线索是食欲以及觅食和摄食行为的有力调节剂。在皮质纹状体、丘脑和下丘脑网络内以独特模式上调的许多早期基因表明，食物线索能够有力地改变调节情绪、认知、觉醒和能量平衡调节的神经元处理。多巴胺能、内啡肽能和 fos 基因表达是食物渴望行为的重要调节遗传途径。描述多种冲动、强迫和成瘾行为的共同遗传前因的一个总称是奖励缺陷综合征（RDS）。由于 COMT 基因的高代谢基因型，缺乏 5-羟色胺能和/或多巴胺能受体且突触多巴胺代谢率增加的个体易患自我治疗任何会激活多巴胺释放的物质或行为，包括酒精、阿片类药物、精神兴奋剂、尼古丁、葡萄糖、赌博、性，甚至过度的互联网游戏等。最后，利用长期多巴胺能激活方法将最终导致一种治疗 RDS 行为的共同安全有效的模式，包括异常的食物和药物渴望行为。
