Ellagic acid reduced nicotine induced withdrawal syndrome in mice

Aims: Because nicotine is eliminated by metabolism to cotinine and it is the rate limitation reaction, it is a potential pharmacological target for future smoking cessation therapies. Ellagic acid (EA) inhibits P450-mediated activation of the many tobacco specific nitrosamines. Thus, in the present study the anxiolytic activity of EA was examined in withdrawal syndrome produced by nicotine exposure cessation in mice.Methods: Mice exposed to nicotine (2 mg/kg, p.o.) for 14 days, were treated with EA and methoxypsoralene (Mtx) (nicotine metabolism specific inhibitor) at 0, 10, 50 and 100 mg/kg respectively on day 15th, simultaneously nicotine exposure cessation starts and after 24 h anxiolytic activity was measured using the elevated plus maze (EPM) test. The number of entries and the time spent in open arms were recorded during a 6-min observation period.Results and conclusions. In the present study, oral administration of EA and Mtx induced an anxiolytic-like effect in mice, since it significantly increased the number of entries and the time spent on EPM open arms compared to nicotine alone treated animals. In conclusion, EA possesses a significant anxiolytic activity equal to that of the nicotine metabolism inhibitor methoxypsoralene. Its mechanism of action is not clear; nevertheless, further research is required to elucidate the detailed mechanism.