与内啡肽缺乏综合征 (EDS) 相关的奖赏回路中内啡肽/多巴胺能机制的分子神经学相关性,Journal of the Neurological Sciences

当前位置： X-MOL 学术 › J. Neurol. Sci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

与内啡肽缺乏综合征 (EDS) 相关的奖赏回路中内啡肽/多巴胺能机制的分子神经学相关性
Journal of the Neurological Sciences ( IF 3.6 ) Pub Date : 2020-04-01 , DOI: 10.1016/j.jns.2020.116733
Kenneth Blum ₁ , David Baron ₁ , Thomas McLaughlin ₂ , Mark S Gold ₃

Affiliation

当前文献的共识强烈支持大脑神经递质和参与中脑边缘区域多巴胺净释放的第二信使，尤其是伏隔核 (NAc)，与动机、抗压力、激励显着性直接相关的概念。想要）和幸福。多巴胺在酒精戒断症状、可卡因渴望行为、多巴胺缩合产物 (TIQ) 以及最近药物寻求和多巴胺前体调节的遗传方面的作用，提供了相关分子神经学相关性的令人信服的证据由于遗传多态性和表观遗传损伤，奖励回路中的多巴胺能/内啡肽机制。面对美国阿片类药物的流行，临床共识是通过终生阿片类药物替代疗法来治疗阿片类药物使用障碍 (OUD)。然而，作者提出了一种范式转变，涉及新的模式，例如在诱导所需的“多巴胺稳态”方面，靶向与 NAc 处多巴胺释放相关的内啡肽系统。利用已知的遗传 - 环境相互作用定理 P = G + E，作者为采用遗传风险测试和内啡肽/多巴胺调节来解决整个大脑奖励回路的功能障碍提供了明确的基本原理。改变静息状态、功能连接的目标可能需要温和的“神经递质修复” vis 抑制脑啡肽酶以克服或对抗 - 通过精神活性物质滥用自我诱导急性多巴胺释放，导致慢性多巴胺下调。作为奖励缺陷的子集，我们准备利用“精确成瘾管理”为内啡肽、阿片类药物和多巴胺能缺陷及相关综合征提供新颖的遗传指导疗法。

"点击查看英文标题和摘要"

Molecular neurological correlates of endorphinergic/dopaminergic mechanisms in reward circuitry linked to endorphinergic deficiency syndrome (EDS)

The consensus of the current literature strongly supports the concept that brain neurotransmitters, and second messengers involved in the net release of dopamine in the mesolimbic region, especially the Nucleus Accumbens (NAc), is directly linked to motivation, anti-stress, incentive salience (wanting), and well-being. The role of dopamine in terms of alcohol withdrawal symptomology, cocaine craving behavior, dopamine -condensation products (TIQs), and more recently, the genetic aspects of drug-seeking and pro-dopamine regulation, provide compelling evidence of the relevant molecular neurological correlates of dopaminergic /endorphinergic mechanisms in reward circuitry due to genetic polymorphisms and epigenetic insults. In the face of an Americans opioid epidemic, the clinical consensus is to treat Opioid Use Disorder (OUD) with life-long opioid substitution therapy. However, the authors suggest a paradigm shift involving novel modalities like targeting the endorphinergic system linked to dopamine release at the NAc, in terms of the induction of required "dopamine homeostasis." Utilizing the known genetic - environmental interaction theorem P = G +E, the authors provide a clear rationale for the adoption of genetic risk testing coupled with endorphinergic/dopamine regulation to address dysfunction across the brain reward circuitry. The goal of altering resting-state, functional connectivity may require a gentle "neurotransmitter fix" vis enkephalinase inhibition to overcome or combat - self-induction of acute dopamine release via psychoactive substance misuse resulting in chronic dopamine down-regulation. As subsets of reward deficiency, we are poised to provide novel, genetically guided therapy for endorphinergic, opioidergic, and dopaminergic deficiencies and related syndromes, utilizing "Precision Addiction Management.

更新日期：2020-04-01

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南