Induction of physical dependence upon ethanol and the associated behavioral changes in rats

This paper reports findings relative to a simple, rapid and reproducible technique for the induction of physical dependence upon ethanol in the rat. The dependence was induced by intragastric intubation of 20% (w/v) ethanol solutions at 9–15 g/kg in 3–5 fractional doses daily for 4 days, maintaining blood ethanol concentrations above a threshold level sufficient to sustain observable sedation throughout the entire period of intubation. Two phases were distinguished during the withdrawal period: 1. Prodromal detoxication, characterized by a spectrum of signs and responses of diminishing severity, related to the decline in blood ethanol concentrations (mg/dl): death, >640; coma, 780–460; loss of righting reflex, 640–440; ataxia 3–1, 570–250; sedation, 340–190; neutrality, 220–130; 2. Ethanol dependence, characterized by a spectrum of withdrawal signs and reactions of progressively increasing severity as blood ehtanol concentration approached 100mg/dl: hyperactivity, tremors, akinesia, spastic rigidity, and induced and spontaneous convulsions. A rapid succession of two diverse clusters of signs and reactions represents a reversal of the central nervous system function from the extremes of ethanol intoxication (CNS depression) to the extremes of ethanol dependence (CNS hyperexcitability) during the withdrawal period. Both extremes may terminate in death.