Quantification of tremor sensitivity and inhibition of exploratory behaviour during alcohol withdrawal in rats

Abstract

Rats given a 10% (v/v) alcohol liquid diet over two weeks reached high blood alcohol levels of around 200mg/dl. Discontinuation of the alcohol intake resulted within 6h in several withdrawal reactions including a tremorogenic activity and a reduction in exploratory behaviour in novel environments. The tremorogenic activity of the alcohol withdrawal could be quantified, using a piezo-film technique, in terms of a supersensitivity to both an inactive and a moderately active dose of the tremorogenic compound harmine. As compared to controls, the rats in alcohol withdrawal revealed more frequent tremor after both 5 and 10mg/kg harmine. The supersensitivity to harmine-induced tremor started within 6h after alcohol withdrawal and remained present with 10mg/kg harmine for up to 48h. The supersensitivity was independent of the length of the tremor bursts used to quantify harmine-induced tremor. Alcohol withdrawal also resulted in an inhibition of exploratory behaviour in a neutral two-chamber box. Both in terms of the number of transits into the open field as well as the time spent in the open area, rats in alcohol withdrawal were significantly less active than control animals. The reduced exploration started within 6h after withdrawal and remained present for up to 24h after the last alcohol intake. These results indicate that both alcohol withdrawal-induced sensitivity to tremorogenic agents and inhibition of exploratory behaviour can be quantified over time, allowing the pharmacological mechanisms involved to be studied.