Traktirov Dmitrii S, Nazarov Ilya R, Artemova Valeria S, Gainetdinov Raul R, Pestereva Nina S, Karpenko Marina N
Department of Physiology (Pavlov's), Institute of Experimental Medicine, 197022 St. Petersburg, Russia.
Faculty of Biology, St. Petersburg State University, 199034 St. Petersburg, Russia.
Biomedicines. 2023 Oct 24;11(11):2881. doi: 10.3390/biomedicines11112881.
Biogenic amines dopamine (DA) and serotonin (5-HT) are among the most significant monoaminergic neurotransmitters in the central nervous system (CNS). Separately, the physiological roles of DA and 5-HT have been studied in detail, and progress has been made in understanding their roles in normal and various pathological conditions (Parkinson's disease, schizophrenia, addiction, depression, etc.). In this article we showed that knockout of the gene encoding DAT leads not only to a profound dysregulation of dopamine neurotransmission in the striatum but also in the midbrain, prefrontal cortex, hippocampus, medulla oblongata and spinal cord. Furthermore, significant changes were observed in the production of mRNA of enzymes of monoamine metabolism, as well as to a notable alteration in the tissue level of serotonin, most clearly manifested in the cerebellum and the spinal cord. The observed region-specific changes in the tissue levels of serotonin and in the expression of dopamine and serotonergic metabolism enzymes in rats with an excess of dopamine can indicate important consequences for the pharmacotherapy of drugs that modulate the dopaminergic system. The drugs that affect the dopaminergic system could potently affect the serotonergic system, and this fact is important to consider when predicting their possible therapeutic or side effects.
生物胺多巴胺(DA)和血清素(5-HT)是中枢神经系统(CNS)中最重要的单胺能神经递质。此前,已分别对DA和5-HT的生理作用进行了详细研究,并且在理解它们在正常及各种病理状况(帕金森病、精神分裂症、成瘾、抑郁症等)中的作用方面取得了进展。在本文中,我们表明,编码多巴胺转运体(DAT)的基因敲除不仅导致纹状体中多巴胺神经传递的严重失调,还导致中脑、前额叶皮质、海马体、延髓和脊髓中多巴胺神经传递的严重失调。此外,观察到单胺代谢酶的mRNA产生有显著变化,血清素的组织水平也有明显改变,最明显表现在小脑和脊髓中。在多巴胺过量的大鼠中观察到的血清素组织水平以及多巴胺和血清素能代谢酶表达的区域特异性变化,可能表明对调节多巴胺能系统的药物进行药物治疗具有重要意义。影响多巴胺能系统的药物可能会强烈影响血清素能系统,在预测其可能的治疗效果或副作用时,这一事实很重要。