Raevskiĭ K S, Narkevich V B, Klodt P M, Kudrin V S
Eksp Klin Farmakol. 2011;74(12):3-7.
Effects of separate and combined introduction of afobazole and SB-200646A (highly selective 5-HT2B/2C receptor antagonist) on the content of monoamines and their metabolites in brain structures of mice of C57/Bl/6 and BALB/C lines have been studied using neurochemical methods and high-performance liquid chromatography (HPLC). Afobazole (5 mg/kg, i.p.) significantly increased dopamine (DA) level in hypothalamus and amygdala of C57/Bl/6 mice, while no changes of DA content were observed in BALB/C mice. At the same time, the concentrations of DA metabolites dioxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the same structures as well as in striatum were decreased compared to control. Afobazole also led to a decrease in the content of 5-hydroxyindoleacetic acid (5-HIAA) and 5-HIAA/5-HT index in frontal cortex and amygdala of C57/Bl/6 mice; analogous decrease in the latter parameter was observed in striatum of BALB/C mice. The introduction of SB-200646A (10 mg/kg, i.p.) almost did not influence the neurochemical indices of the content and metabolism of monoamines, except for an increase in the HVA content in amygdala and the DOPAC and 5-HIAA concentrations in striatum of C57/Bl/6 mice. The joint introduction of afobazole and SB-200646A led to an increase in the content of norepinephrine (NE) in striatum of BALB/C mice and in hippocamp of mice of both lines. The data obtained may be indicative of the involvement of NE- and DA-ergic neurotransmitter systems in the mechanisms of afobazole action. Enhanced anxiolytic effect of the joint introduction of afobazole and SB-200646A can be interpreted as a positive modulation of the anxiolytic drug action related to the blocking of 5-HT2-type serortonin receptors. The results also reveal inter-line differences of neurochemical responses induced by combination of afobazole and selective antagonist of serotonin.
运用神经化学方法和高效液相色谱法（HPLC），研究了分别及联合给予阿伏苯唑和SB - 200646A（高选择性5 - HT2B/2C受体拮抗剂）对C57/Bl/6和BALB/C系小鼠脑结构中单胺及其代谢产物含量的影响。阿伏苯唑（5毫克/千克，腹腔注射）显著提高了C57/Bl/6小鼠下丘脑和杏仁核中的多巴胺（DA）水平，而BALB/C小鼠的DA含量未观察到变化。同时，与对照组相比，相同结构以及纹状体中DA代谢产物二羟基苯乙酸（DOPAC）和高香草酸（HVA）的浓度降低。阿伏苯唑还导致C57/Bl/6小鼠额叶皮质和杏仁核中5 - 羟吲哚乙酸（5 - HIAA）含量及5 - HIAA/5 - HT指数降低；在BALB/C小鼠的纹状体中也观察到后一参数有类似降低。给予SB - 200646A（10毫克/千克，腹腔注射）几乎不影响单胺含量和代谢的神经化学指标，除了C57/Bl/6小鼠杏仁核中HVA含量增加以及纹状体中DOPAC和5 - HIAA浓度增加。阿伏苯唑和SB - 200646A联合给予导致BALB/C小鼠纹状体以及两系小鼠海马中去甲肾上腺素（NE）含量增加。所得数据可能表明NE能和DA能神经递质系统参与了阿伏苯唑的作用机制。阿伏苯唑和SB - 200646A联合给予增强的抗焦虑作用可解释为与5 - HT2型血清素受体阻断相关的抗焦虑药物作用的正向调节。结果还揭示了阿伏苯唑与血清素选择性拮抗剂联合使用所诱导的神经化学反应的品系间差异。
