Anxiolytic effect of a herbal medicine, yokukansan, in aged rats: Involvement of serotonergic and dopaminergic transmissions in the prefrontal cortex

Abstract

Aim of the study Aging is thought to affect emotions including anxiety, and a herbal medicine, yokukansan (YKS), is used to treat emotional disturbances associated with age-related neurodegenerative disorders such as Alzheimer's disease, but its pharmacological properties have not been fully understood. The present study was designed to examine whether YKS improves age-related anxiety using F344/N aged rats. Moreover, the effects of YKS on liver function were examined. Materials and methods YKS was administered to 21-month-old aged rats for 3 months. Locomotor activity of young control (4 months old), aged control (24 months old), and YKS-treated aged rats was examined, and the anxiety-related responses of these animals were evaluated by counting the number of excrements during locomotor activity measurement and in the elevated plus-maze test. The extracellular concentrations of serotonin and dopamine in the prefrontal cortex (PFC) were also measured using a microdialysis technique. Moreover, concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and ammonia (NH 3) in plasma were measured. Results Although locomotor activity did not change among any experimental groups, the number of excrements was significantly increased in aged rats compared to young rats, and this increase was significantly improved by YKS treatment. Aged rats also showed significant decreases in time and frequency in the open arm of the elevated plus-maze, and these decreases were significantly improved by YKS treatment. Extracellular concentrations of serotonin and dopamine in the aged PFC were significantly decreased; serotonin was increased over the level of young rats and dopamine was partially improved by YKS treatment, respectively. In addition, YKS improved age-related increase in NH 3 concentration, but did not affect AST and ALT. Conclusions YKS has improving activity for age-related increased anxiety and enhances serotonergic and dopaminergic transmissions in the aged PFC. These mechanisms provide information important for the treatment of anxiety in the elderly. Furthermore, the present data confirm partially the Kampo concept “liver disease”.