Increased sensitivity to picrotoxin as an index of physical dependence on alcohol in the mouse

A relatively simple and rapid method has been developed to induce tolerance to and dependence on alcohol in mice. Alternating intraperitoneal injections of metabolically stable tert-butanol and ethanol for 4 consecutive days resulted in a physical dependence on alcohol, which was quantified by the latency and ED₅₀ of picrotoxin-induced CNS hyperexcitability — myoclonic and tonic seizures and mortality — during the withdrawal period. The data indicate that alcohol-dependent animals in the withdrawal period are more susceptible than alcohol-naive controls to picrotoxin. Withdrawal hyperexcitability can be quantified by the ED₅₀ of picrotoxin.