Rayevsky K S, Narkevich V B, Klodt P M, Kudrin V S
Laboratory of Neurohistology, PK Anokhin Institute of Normal Physiology, Russian Academy of Medical Sciences, Moscow, Russia.
Bull Exp Biol Med. 2012 Sep;153(5):689-93. doi: 10.1007/s10517-012-1800-y.
The effects of combined administration of afobazole and 5-HT(2b/2c)receptor antagonist SB-200646A on the content of monoamines and their metabolites in brain structures of C57Bl/6 and BALB/c mice were studied by the methods of HPLC with electrochemical detection. Combined administration of afobazole and SB-200646A increased the content of epinephrine in the striatum of BALB/c mice (to 230% of the control) and in the hippocampus of both mouse strains. The content of dihydroxyphenylacetic and homovanillic acids and parameters of dopamine metabolism in these structures were reduced. The content of dopamine in the hypothalamus and amygdala was elevated in C57Bl/6, but not in BALB/c mice. These findings attest to the involvement of monoamine systems of the brain in the mechanism of afobazole action and suggest that the enhanced anxiolytic effect of afobazole combination with SB-200646A can be interpreted as a positive modulation of the effect of anxiolytic determined by blockade of 5-HT(2)serotonin receptors.
采用高效液相色谱电化学检测法,研究了阿伏唑与5-羟色胺(2b/2c)受体拮抗剂SB - 200646A联合给药对C57Bl/6和BALB/c小鼠脑结构中单胺及其代谢产物含量的影响。阿伏唑与SB - 200646A联合给药使BALB/c小鼠纹状体中的肾上腺素含量增加(达到对照组的230%),并使两种品系小鼠海马体中的肾上腺素含量增加。这些结构中二羟基苯乙酸和高香草酸的含量以及多巴胺代谢参数降低。C57Bl/6小鼠下丘脑和杏仁核中的多巴胺含量升高,但BALB/c小鼠未出现这种情况。这些发现证明大脑单胺系统参与了阿伏唑的作用机制,并表明阿伏唑与SB - 200646A联合使用增强的抗焦虑作用可解释为通过阻断5-羟色胺(2)血清素受体对抗焦虑作用的正向调节。