Alcantara Adriana A, Chen Violeta, Herring Bruce E, Mendenhall John M, Berlanga Monica L
Institute for Neuroscience, The University of Texas at Austin, Austin, TX 78712, USA.
Brain Res. 2003 Oct 3;986(1-2):22-9. doi: 10.1016/s0006-8993(03)03165-2.
Striatal cholinergic interneurons located in the dorsal striatum and nucleus accumbens are amenable to influences of the dopaminergic mesolimbic pathway, which is a pathway involved in reward and reinforcement and targeted by several drugs of abuse. Dopamine and acetylcholine neurotransmission and their interactions are essential to striatal function, and disruptions to these systems lead to a variety of clinical disorders. Dopamine regulates acetylcholine release through dopamine receptors that are localized directly on striatal cholinergic interneurons. The dopamine D2 receptor, which attenuates acetylcholine release, has been implicated in drug relapse and is targeted by therapeutic drugs that are used to treat a variety of neurological disorders including Tourette Syndrome, Parkinson's disease and schizophrenia. The present study provides the first direct evidence for the localization of dopamine D2 receptors on striatal cholinergic interneurons of the rat brain using dual labeling immunocytochemistry procedures. Using light microscopy, dopamine D2 receptors were localized on the cell somata and dendritic and axonal processes of striatal cholinergic interneurons in the dorsal striatum and nucleus accumbens of the rat brain. These findings provide a foundation for understanding the specific roles that cholinergic neuronal network systems and interacting dopaminergic signaling pathways play in striatal function and in a variety of clinical disorders including drug abuse and addiction.
位于背侧纹状体和伏隔核的纹状体胆碱能中间神经元易受多巴胺能中脑边缘通路的影响，该通路参与奖赏和强化过程，且是多种滥用药物的作用靶点。多巴胺和乙酰胆碱神经传递及其相互作用对纹状体功能至关重要，这些系统的破坏会导致多种临床疾病。多巴胺通过直接位于纹状体胆碱能中间神经元上的多巴胺受体调节乙酰胆碱的释放。抑制乙酰胆碱释放的多巴胺D2受体与药物复吸有关，并且是用于治疗包括妥瑞氏症、帕金森病和精神分裂症在内的多种神经系统疾病的治疗药物的作用靶点。本研究使用双重标记免疫细胞化学方法，首次为多巴胺D2受体在大鼠脑纹状体胆碱能中间神经元上的定位提供了直接证据。通过光学显微镜观察，多巴胺D2受体定位于大鼠脑背侧纹状体和伏隔核中纹状体胆碱能中间神经元的细胞体、树突和轴突上。这些发现为理解胆碱能神经元网络系统和相互作用的多巴胺能信号通路在纹状体功能以及包括药物滥用和成瘾在内的多种临床疾病中所起的特定作用奠定了基础。
