Induction of physical dependence on alcohol in rodents.

An ethanol withdrawal syndrome consisting of tremors and seizures can be induced in rats and mice. This syndrome closely resembles the physical signs observed in human patients during alcohol withdrawal. The criteria for an animal model of a human disease appear to be fulfilled regarding the etiological agent, course of illness, the similarity of physical and electrophysiological manifestations and response to therapeutic agents. Therefore these models should lend themselves for the elucidation of the pathogenesis at the molecular level of biological organization and for the development of new therapeutic approaches. Criteria for an optimal animal model of ethanol dependence are outlined. Withdrawal signs are classified into minor (startle threshold and exploratory behavior) and major types (tremors and seizures). Methods for quantification of tremors and seizures are described. The procedures for induction of the major withdrawal signs are classified according to the mode of ethanol administration designed to circumvent the animal's inherent aversion to the taste of ethanol: Oral (free feeding, behavioral modifications of free feeding and force feeding), parenteral and inhalation. Auxiliary procedures consist of pyrazole administration and weight reduction resulting in a decreased rate of ethanol metabolism. Exposure to low environmental temperatures increases consumption of ethanol containing diets without proportionately increasing the rate of ethanol metabolism. Auxiliary procedures for the induction of seizures during withdrawal consist of handling the animals and audiogenic stimuli. Advantages and limitations of various rodent models are evaluated in terms of the procedures (practicability, compounding variables) and their results (reproducibility, severity and yield of major withdrawal signs, objective quantification). It is concluded that none of the current methods fulfill all requisites for all types of experiments. The selection of methods best suited for a particular experiment depend upon its objectives.