Possible nitric oxide mechanism involved in the protective effect of L-theanine on haloperidol-induced orofacial dyskinesia.

Having powerful antioxidative properties, L-theanine (LT), one of the major amino acid components in green tea, has potent anti-oxidative and neuroprotective effects. In this study, we examined the potential protective effects of LT on haloperidol (HAL)-induced orofacial dyskinesia (OD) in rats. HAL treatment (1 mg/kg intraperitoneally for 21 days) induced OD; significant increases (P < 0.001) in the frequency of vacuous chewing movement and tongue protrusion as well as the duration of facial twitching. LT treatment (100 mg/kg orally for 35 days, starting 14 days before HAL injection) was able to prevent most of the HAL-induced OD. LT treatment was also able to reduce the lipid peroxidation production and nitric oxide (NO) level, and enhance the antioxidation power in striatum from rats with HAL treatment. In order to examine the implication of NO pathway activity in HAL treatment, either NO precursor (L-arginine) or NO synthase inhibitor (L-NAME) was co-pretreated with LT; NO precursor treatment eliminated the protective effect of LT, in contrast to that NO synthase inhibitor treatment significantly potentiated the LT effects on behavioral and biochemical protection in HAL-treated rats. These results suggested that the NO pathway was implicated, at least in part, in the HAL-induced OD, as well as in the protective effect of LT in treating HAL-induced OD. The above evidence provides a clinically relevant value for LT in delaying or treating tardive dyskinesia.