Ameliorative effect of yokukansan on vacuous chewing movement in haloperidol-induced rat tardive dyskinesia model and involvement of glutamatergic system.

Effects of yokukansan (YKS) on vacuous chewing movement (VCM), which is an index for tardive dyskinesia, were investigated in haloperidol decanoate-treated rats. Haloperidol decanoate was injected to a thigh muscle once every four weeks for 18 weeks. The rats which exhibited VCM eight times or more in 3min were selected on the 12th week, and examined. A significant increase in VCM on the 12th week continued until the 18th week. Oral administration of YKS (0.1 and 0.5g/kg) once a day for three weeks (21 days) from the 12th week to 15th week ameliorated the haloperidol decanoate-induced increase in VCM in a dose-dependent manner. The significant ameliorative effect observed in 0.5g/kg YKS-treated rats was abolished by stopping administration for three weeks from the 15th week to the 18th week. The extracellular glutamate concentration and glutamate transporter mRNA expression in the striatum were evaluated by microdialysis and real-time reverse-transcription polymerase chain reaction assays at the 15th week. The striatal glutamate level increased in haloperidol-treated rats, and the increase was inhibited by treatment with YKS. The striatal GLT-1 mRNA level showed a tendency to decrease in the haloperidol-treated rats. The GLT-1 mRNA level after treatment with YKS (0.5g/kg) was greater than the control level. These results suggest the effect of YKS may be involved in the extracellular glutamate level and GLT-1 mRNA expression in the striatum.