Abstract—We studied the neurochemical effects of afobazol in the brain structures of BALB/C and C57BL/6 mice with serotonin deficit induced by para-chlorophenylalanine (PCPA), which inhibits tryptophan 5‑hydroxylase, the main enzyme of serotonin synthesis. Interstrain differences were found in the level of norepinephrine (NE), serotonin (5-HT), and dopamine (DA) metabolism parameters in the frontal cortex (FC), amygdala, striatum, hypothalamus, and hippocampus. It was demonstrated that PCPA (350 mg/kg/3 days) caused a considerable decrease in the level of 5-HT and its metabolite 5-HIAA in the structures of the brain studied in both strains of mice, but in BALB/C mice the decrease in these indices was more intense (2–2.5 times). PCPA decreased the level of NE in the hypothalamus, amygdala, and striatum of C57BL/6 mice. In the 5-HT deficiency model, afobazol (5 mg/kg) influenced the parameters of dopaminergic neurotransmission by decreasing the level of DOPAC and the DOPAC/DA ratio in the hypothalamus and striatum of both strains. An increase in the content of 5-HT and NE was observed after a decrease caused by the administration of PCPA in the hypothalamus and amygdala of BALB/C mice and the hippocampus and amygdala of C57BL/6 mice. The indices of 5-HIAA/5-HT metabolism rate were decreased. The results of the current study confirm the previous data on the role of the serotonergic brain systems in the mechanism of action of afobazol. In PCPA-induced serotonin deficit, the drug influenced both stress-resistant (C57BL/6) and more emotionally labile animals (BALB/C) which is reflected by the restoration of serotonin and norepinephrine levels in the hypothalamus of BALB/C mice, as well as in the amygdala and hippocampus of C57BL/6 strain.

摘要—我们研究了阿夫巴唑对BALB / C和C57BL / 6小鼠脑组织结构的神经化学作用，这些小鼠由对乙酰氨基酚引起5-羟色胺缺乏-氯苯丙氨酸（PCPA），它抑制色氨酸5-羟化酶（5-羟色胺合成的主要酶）。在额叶皮质（FC），杏仁核，纹状体，下丘脑和海马中，去甲肾上腺素（NE），5-羟色胺（5-HT）和多巴胺（DA）代谢参数的水平之间存在差异。结果表明，在两种小鼠品系中，但在BALB / C小鼠中，PCPA（350 mg / kg / 3天）导致所研究的大脑结构中5-HT水平及其代谢产物5-HIAA的显着降低。这些指数的下降幅度更大（2-2.5倍）。PCPA降低了C57BL / 6小鼠的下丘脑，杏仁核和纹状体中NE的水平。在5-HT缺乏症模型中 afobazol（5 mg / kg）通过降低两种菌株下丘脑和纹状体中的DOPAC含量和DOPAC / DA比来影响多巴胺能神经传递的参数。在BALB / C小鼠的下丘脑和杏仁核以及C57BL / 6小鼠的海马和杏仁核中施用PCPA引起的减少后，观察到5-HT和NE含量的增加。5-HIAA / 5-HT代谢率指标降低。当前研究的结果证实了先前有关5-羟色胺能脑系统在阿夫巴唑作用机制中的作用的数据。在PCPA诱导的5-羟色胺缺乏症中，该药物影响了抗应激性（C57BL / 6）和情绪较不稳定的动物（BALB / C），这可以通过BALB / C小鼠下丘脑中5-羟色胺和去甲肾上腺素水平的恢复反映出来，