Department of Psychology, The University of Memphis, TN, USA.
CNS Neurosci Ther. 2010 Jun;16(3):137-62. doi: 10.1111/j.1755-5949.2010.00142.x. Epub 2010 Mar 29.
Dopaminergic neurons in the substantia nigra pars compacta and ventral tegmental area of the midbrain form the nigrostriatal and mesocorticolimbic dopaminergic pathways that, respectively, project to dorsal and ventral striatum (including prefrontal cortex). These midbrain dopaminergic nuclei and their respective forebrain and cortical target areas are well established as serving a critical role in mediating voluntary motor control, as evidenced in Parkinson's disease, and incentive-motivated behaviors and cognitive functions, as exhibited in drug addiction and schizophrenia, respectively. Although it cannot be disputed that excitatory and inhibitory amino acid-based neurotransmitters, such as glutamate and GABA, play a vital role in modulating activity of midbrain dopaminergic neurons, recent evidence suggests that acetylcholine may be as important in regulating dopaminergic transmission. Midbrain dopaminergic cell tonic and phasic activity is closely dependent upon projections from hindbrain pedunculopontine and the laterodorsal tegmental nuclei, which comprises the only known cholinergic inputs to these neurons. In close coordination with glutamatergic and GABAergic activity, these excitatory cholinergic projections activate nicotinic and muscarinic acetylcholine receptors within the substantia nigra and ventral tegmental area to modulate dopamine transmission in the dorsal/ventral striatum and prefrontal cortex. Additionally, acetylcholine-containing interneurons in the striatum also constitute an important neural substrate to provide further cholinergic modulation of forebrain striatal dopaminergic transmission. In this review, we examine neurological and psychopathological conditions associated with dysfunctions in the interaction of acetylcholine and dopamine and conventional and new pharmacological approaches to treat these disorders.
中脑黑质致密部和腹侧被盖区的多巴胺能神经元形成黑质纹状体和中皮质边缘多巴胺能通路，分别投射到背侧和腹侧纹状体（包括前额叶皮层）。这些中脑多巴胺能核及其各自的前脑和皮质靶区被认为在介导自愿运动控制方面发挥着关键作用，这在帕金森病中得到了证明，以及激励动机行为和认知功能，分别在药物成瘾和精神分裂症中表现出来。尽管兴奋性和抑制性氨基酸基神经递质，如谷氨酸和 GABA，在调节中脑多巴胺能神经元的活动中起着至关重要的作用，这是不可否认的，但最近的证据表明，乙酰胆碱在调节多巴胺传递中可能同样重要。中脑多巴胺能细胞的紧张和相位活动密切依赖于来自后脑脑桥被盖和外侧背盖核的投射，这是这些神经元唯一已知的胆碱能输入。与谷氨酸能和 GABA 能活动密切协调，这些兴奋性胆碱能投射激活尼古丁和毒蕈碱乙酰胆碱受体在黑质和腹侧被盖区调节背侧/腹侧纹状体和前额叶皮层中的多巴胺传递。此外，纹状体中的含乙酰胆碱的中间神经元也是提供前脑纹状体多巴胺能传递进一步胆碱能调节的重要神经基质。在这篇综述中，我们研究了与乙酰胆碱和多巴胺相互作用功能障碍相关的神经和精神病理学状况，以及治疗这些疾病的传统和新的药理学方法。
