Department of Pharmacology, Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho-Nishi, Matsudo, Chiba, 271-8587, Japan.
School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin 2, Ireland.
Pharmacol Rep. 2021 Aug;73(4):971-983. doi: 10.1007/s43440-021-00249-9. Epub 2021 Mar 20.
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 GABA and GABA receptors 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.
伏隔核（NAc）是腹侧被盖区中脑边缘多巴胺（DA）神经元投射的末端区域。Accumbal DA 的释放由来自其他脑区的传入和中间神经元整合，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发病机制，是通过受体亚型介导的，其在调节 Accumbal DA 释放中的相对作用尚不清楚。这种复杂的相互作用的一个例子是，阿片受体亚型的选择性激活如何以通过 GABA 受体亚型改变神经活动来调节的方式增强 Accumbal DA 的外排。本综述描述了 GABA 和 GABA 受体在 NAc 中的 GABA 能神经机制中的作用，这些机制参与了在自由活动的大鼠中 δ 和 μ 阿片受体介导的 Accumbal DA 外排的增加，重点研究了使用体内脑微透析的研究。首先，我们考虑内源性 GABA 通过 GABA 受体亚型如何发挥对 Accumbal DA 外排的抑制作用。我们还考虑了抑制 Accumbal DA 外排的内源性 GABA 的可能神经元内来源。由于 NAc 包含表达 δ 或 μ 阿片受体的 GABA 能神经元，因此抑制 Accumbal GABA 能神经元是介导 δ 或 μ 阿片受体介导的 Accumbal DA 外排增加的候选物。因此，我们详细分析了 GABA 受体亚型配体对 δ 和 μ 阿片受体介导的 Accumbal DA 外排的影响。最后，我们提出了一个综合模型，以解释 NAc 中 δ 和 μ 阿片受体、GABA 能神经元和 DA 能神经元之间相互作用的机制。
