Raevskiĭ K S, Sotnikova T D, Gaĭnetdinov R R
Usp Fiziol Nauk. 1996 Oct-Dec;27(4):3-29.
Recent advances in molecular neurobiology led to a new understanding on mammalian brain dopaminergic system which play a major role in the regulation of motor, cognitive, emotional, neuroendocrine function as well as in the pathogenesis of several pathological conditions, including neurodegenerative diseases, affective disorders, schizophrenia, drug addiction etc. Functional, biochemical and pharmacological heterogeneity of dopamine receptors, which were divided into D1-like (D1 and D5 subtypes) and D2-like (D2, D3 and D4) families of receptors has been postulated. The article reviews the recent advances including author's own results concerning the structure and function of main dopaminergic brain system, i.e. nigrostriatal and mesolimbic. The problem of autoreceptor regulation of dopaminergic neurotransmission, particularly, the processes of dopamine synthesis, release and metabolism has been specially discussed. An involvement of D2 and D3 dopamine autoreceptors in the control of these processes and differences in the mode of action of typical and atypical neuroleptics demonstrating various affinities to D2 and D3 dopamine receptors are analysed in detail. Dopamine and its metabolites have been determined on freely moving rats using brain microdialysis and high performance liquid chromatography. It is hypothesized that dopamine D3 autoreceptor is preferentially involved in the regulation of dopamine release while D2 one is responsible for the control of dopamine synthesis and metabolism in rat basal ganglia in vivo.
分子神经生物学的最新进展使人们对哺乳动物脑多巴胺能系统有了新的认识,该系统在运动、认知、情感、神经内分泌功能的调节以及包括神经退行性疾病、情感障碍、精神分裂症、药物成瘾等多种病理状况的发病机制中起主要作用。多巴胺受体存在功能、生化和药理学异质性,已假定其分为D1样(D1和D5亚型)和D2样(D2、D3和D4)受体家族。本文综述了包括作者本人关于主要脑多巴胺能系统,即黑质纹状体和中脑边缘系统的结构与功能的最新研究成果。特别讨论了多巴胺能神经传递的自身受体调节问题,尤其是多巴胺合成、释放和代谢过程。详细分析了D2和D3多巴胺自身受体在这些过程控制中的作用,以及典型和非典型抗精神病药物对D2和D3多巴胺受体具有不同亲和力的作用方式差异。利用脑微透析和高效液相色谱法测定了自由活动大鼠体内的多巴胺及其代谢产物。据推测,多巴胺D3自身受体优先参与多巴胺释放的调节,而D2自身受体负责在体内大鼠基底神经节中控制多巴胺的合成和代谢。