European Journal of Biomedical and Pharmaceutical Sciences

EVALUATION OF KYNURENIC ACID ATTENUATES ETHANOL WITHDRAWAL INDUCED HYPEREXCITABILITY IN MICE

K.V. Ambulkar, P.C. Patle, D. T. Gautam*, C. R. Tenpe, S. S. Rathod, V. S. Mule, A. M. Patole, V. A. Jagtap

ABSTRACT

The present study was undertaken to investigate the effects of kynurenic acid attenuates hyperexcitability after ethanol withdrawal in mice. Acute and chronic administration of both kynurenic acid and diazepam (or saline) which mice exhibited peak ethanol withdrawal-induced hyper excitability. Treatment with kynurenic acid (50 or 100 mg/kg, i.p.), 30 min prior to peak ethanol withdrawal-induced hyper excitability signs (7 h), significantly reduced ethanol withdrawal-induced hyper excitability sign scores compared with the vehicle treated group, whereas a lower dose (50 mg/kg, i.p.) did not influence the ethanol withdrawal-induced signs. In other experiments, administration of diazepam (1.25 or 2.5 mg/kg, i.p.), 30 min prior to peak (7 h), dose-dependently attenuated the withdrawal signs, whereas a lower dose (0.625 mg/kg, i.p.) did not influence the ethanol withdrawal-induced signs. Acute treatment with kynurenic acid and diazepam in the control liquid-diet groups had no influence on the physical signs of hyper excitability. In line with the above, it was observed that acute effect of kynurenic acid did not show any significant effect on locomotor. The significant effects on locomotor activity compared with the Vehicle treated animals. In contrast, diazepam (2.5 mg/kg, i.p.) significantly reduced chronic treatment with kynurenic acid exhibited prevention in hyper locomotor effect of ethanol withdrawal. The results and evidence suggest that kynurenic acid exhibited an inhibitory influence against ethanol withdrawal-induced hyper excitability signs which could be mediated through its neuromodulatory & neuroprotective action.

Keywords: Kynurenic acid, Hyperexcitability, Ethanol Withdrawal, NMDA Receptor.