The efficacy of Egb761 on haloperidol-induced tardive dyskinesia model male rats and possible mechanism

Abstract

Objective To investigate the efficacy of Egb761 on vacuous chewing movements (VCMs) of haloperidol-induced tardive dyskinesia (TD) rats and serum levels of brain-derived neurotrophic factor (BDNF) and total antioxidant capacity (TAC), and to explore the possible mechanism of treatment. Methods Thirty-two male Sprague-Dawley (SD) rats were randomly divided into the normal saline (NS), TD, Egb761, vitamin E (VitE) group (n=8), processed with NS, haloperidol + NS, haloperidol + Egb761, haloperidol + VitE with 8 rats in each group, the test duration was 10 weeks. VCM was evaluated at each weekend. Venous blood was collected at the end of 10th week, and the serum levels of BDNF and TAC were assayed. Results (1) VCM score of TD, Egb761, VitE group increased gradually after two weeks and reached the peak at the 5th weekend, and they were significantly higher compared with that of NS group (F= 8.96, P 0.05);(2) At the 10th weekend, serum BDNF((6.9±1.0) ng/L), TAC((11.9±3.2) mU/L) levels of TD group were significantly lower than that of the NS ((8.6±2.5) ng/L, (18.2± 5.5) mU/L),Egb761((8.9 ± 1.5) ng/L, (19.4 ± 4.4) mU/L) and VitE group ((8.7 ± 2) ng/L, (18.6 ± 5.9) mU/L). Serum BDNF and TAC levels of the two groups were higher than that of TD group (F=4.21,F=6.67,P 0.05); (3) BDNF serum concentrations were related to the TAC levels (r=0.689,P<0.05) in NS group, however, relationships were not found among the other 3 groups. Conclusions Egb761 and VitE could significantly alleviate VCM score in TD model rats, and decreases of the neurotrophic factors and abnormal metabolism of the free radicals might play a role in etiology of TD. Key words: Dyskinesia, drug-induced; Brain-derived neurotrophic factor; Vitamin E; Egb761; Total antioxidant capacity