DEVELOPMENT OF TOLERANCE TO AND PHYSICAL DEPENDENCE ON BARBITURATES IN RHESUS MONKEYS

¹ Central Institute for Experimental Animals, Medical Research Laboratory, Nogawa, Kawasaki, Japan

Tolerance to and physical dependence on barbiturates was developed in rhesus monkeys by p.o. and parenteral administration. With i.v. administration, strong physical dependence can be developed within two weeks. Major abstinence signs observed in monkeys physically dependent on barbiturates were apprehension, hyperirritabiity, mild tremors, anorexia and piloerection (mild grade); severe tremors, muscle rigidity, impaired motor activity, retching or vomiting and weight loss of over 10% (intermediate); grand mal convulsions, delirium and hyperthermia (severe). Delirium was observed more frequently at night. The rapid development of physical dependence required progressive incrementation of total daily doses to parallel tolerance development in order to maintain maximal central nervous system depression consistent with the health of the animal. This was more critical than any single factor such as duration of drug administration, differences in agent, route of administration or relative dose.

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