The reinforcing property of ethanol in the rhesus monkey. I. Initiation, maintenance and termination of intravenous ethanol-reinforced responding.

Monkeys self-administer pharmacologically significant amounts of alcohol only under certain circumstances.8 For example, Deneau and colleagues' used a method that permitted a rhesus monkey to voluntarily self-administer ethanol solution through an indwelling venous catheter. They found that three of five monkeys initiated and maintained response-contingent deliveries of ethanol at a dose of 200 mg/kg/inj; a fourth monkey initiated self-administration but discontinued spontaneously after one month; and the fifth monkey failed to initiate this behavior even after four weeks of programmed injections of 200 mg/kg/hr of ethanol. Periodic voluntary abstinence was characteristic of the three animals that maintained self-administration. The periods of cessation decreased in length from two to four days to seldom more than 24 hours with the passage of time. During self-administration, monkeys showed severe motor incoordination and stupor. In these alcohol-dependent animals, withdrawal signs appeared within six hours of the last dose of ethanol and consisted of tremors, vomiting, apparent hallucinatory behavior, and convulsions. Food intake throughout the course of the experiment was minimal, and all monkeys showed a marked loss of weight and cachexia. Two of the monkeys died because of suffocation from respiratory obstruction during ethanol-induced anesthesia. The fact that monkeys will self-administer alcohol under these conditions might be viewed as (1) some direct or indirect consequence of physiological dependence (e.g. animals continue to administer alcohol to prevent the appearance of abstinence signs) and/or as (2) evidence that alcohol is behaving as a primary reinforcer (i.e., an effect of alcohol serves to increase or maintain the strength of responding that delivers the drug). A rigorous interpretation is clouded by the reluctance of some animals to self-administer ethanol and by the occurrence of periodic termination of responding, despite withdrawal signs. In an attempt to relate these facts to the reinforcing property of ethanol, we suggest that there is a threshold for alcohol reinforcement and that chronic excessive doses of ethanol produce conditions that override the reinforcing property of the drug. As will be clear from our observations, there is a set of circumstances in chronic ethanol self-administration whereby voluntary abstinence occurs with ensuing withdrawal; otherwise the toxicity of ethanol is sufficient to produce gross illness and even death. In a previous publication' the authors reviewed various techniques of animal self-administration of alcohol and described their own experiments with rhesus