Berberine protects C57BL/6J mice against ethanol withdrawal-induced hyperexcitability

Berberine ([C20H18NO4](+) ), one of the major constituents of the Chinese herb Rhizoma coptidis, is an isoquinoline alkaloid. Plethora of recent reports has indicated its ability to modulate several neurotransmitter systems, especially those implicated in ethanol dependence. Thus, the influence of berberine treatment on the development and expression of ethanol dependence was tested by using the ethanol withdrawal-induced hyperexcitability paradigm. Mice were provided with a nutritionally balanced control liquid diet as the sole nutrient source on day 0; from day 1-4 (ethanol, 3% v/v), from day 5-7 (ethanol, 6% v/v) and from day 8-10 (ethanol, 10% v/v) was incorporated into the liquid diet. On day 11, the ethanol liquid diet was replaced with nutritionally balanced control liquid diet, and ethanol withdrawal-induced hyperexcitability signs were recorded. The results revealed that acute administration of berberine (10 and 20 mg/kg, i.p.) dose-dependently attenuated ethanol withdrawal-induced hyperexcitability signs, and these results were comparable to diazepam (1.25 and 2.5 mg/kg, i.p.). Further, chronic administration of berberine (10 and 20 mg/kg, i.p.) to the ethanol diet fed mice markedly attenuated the ethanol withdrawal-induced hyperexcitability signs. In conclusion, the results and evidence suggest that berberine exhibited an inhibitory influence against ethanol withdrawal-induced hyperexcitability signs, which could be mediated through its neuromodulatory action.