Integrative opioid-GABAergic neuronal mechanisms regulating dopamine efflux in the nucleus accumbens of freely moving animals
Integrative opioid-GABAergic neuronal mechanisms regulating dopamine efflux in the nucleus accumbens of freely moving animals
复制标题
综合阿片类药物-GABA能神经元机制调节自由活动动物伏核中的多巴胺流出
DOI：
10.1007/s43440-021-00249-9
复制
发表时间：
2021
影响因子：
4.4
通讯作者：
Waddington John L.
中科院分区：
文献类型：
--
作者：
Saigusa Tadashi;Aono Yuri;Waddington John L.
中脑腹侧被盖核（NAc）是中脑皮质边缘多巴胺（DA）神经元投射的终末区。Accumbal DA释放由来自其他脑区的传入神经和中间神经元整合，中间神经元涉及多种神经递质和神经肽。这些整合过程，涉及神经精神疾病的病理生物学，介导的受体亚型的相对作用，在调节多巴胺的释放是知之甚少。这种复杂的相互作用是通过阿片受体亚型的选择性激活如何以通过GABA受体亚型的神经活动变化来调节的方式增强脑内DA流出来举例说明的。本文综述了GABA A和GABA B受体在NAc GABA能神经机制中的作用，这些机制参与了δ和μ阿片受体介导的自由活动大鼠多巴胺外排增加，重点是使用在体脑微透析的研究。首先，我们考虑内源性GABA如何通过GABA受体亚型抑制多巴胺的外排。我们还考虑了可能的内源性GABA的神经元内源，抑制多巴胺流出。由于NAc含有表达δ-或μ-阿片受体的GABA能神经元，因此抑制延髓GABA能神经元是介导δ-或μ-阿片受体介导的延髓DA流出增加的候选者。因此，我们提供了一个详细的分析GABA受体亚型配体对δ和μ阿片受体介导的多巴胺外排的影响。最后，我们提出了一个整合模型来解释δ和μ阿片受体，GABA能神经元和DA能神经元之间的相互作用的机制在NAc。
The nucleus accumbens (NAc) is a terminal region of mesocorticolimbic dopamine (DA) neuronal projections from the ventral tegmental area. Accumbal DA release is integrated by afferents from other brain regions and by interneurons, which involve a diversity of neurotransmitters and neuropeptides. These integrative processes, implicated in the pathobiology of neuropsychiatric disorders, are mediated via receptor subtypes whose relative roles in the regulation of accumbal DA release are poorly understood. Such complex interactions are exemplified by how selective activation of opioid receptor subtypes enhances accumbal DA efflux in a manner that is modulated by changes in neural activity through GABA receptor subtypes. This review delineates the roles of GABAAand GABABreceptors in GABAergic neural mechanisms in NAc that participate in delta- and mu-opioid receptor-mediated increases in accumbal DA efflux in freely moving rats, focusing on studies using in vivo brain microdialysis. First, we consider how endogenous GABA exerts inhibition of accumbal DA efflux through GABA receptor subtypes. We also consider possible intra-neuronal source of the endogenous GABA that inhibits accumbal DA efflux. As NAc contains GABAergic neurons that express delta- or mu-opioid receptors, inhibition of accumbal GABAergic neurons is a candidate for mediating delta- or mu-opioid receptor-mediated increases in accumbal DA efflux. Therefore, we provide a detailed analysis of the effects of GABA receptor subtype ligands on delta- and mu-opioid receptor-mediated accumbal DA efflux. Finally, we present an integrative model to explain the mechanisms of interaction among delta- and mu-opioid receptors, GABAergic neurons and DAergic neurons in NAc.