[Possible role of serotonin 5-HT2 receptors in mechanism of afobazole anxiolytic action: neurochemical study of inter-line differences in mice].

ABSTRACT

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.