A primate model for the study of hallucinogens.

Abstract

An animal model for studying the actions of hallucinogenic drugs using primate social colonies is presented. Although hallucinogens induce a number of behavioral changes in this paradigm, one emergent behavior, limb jerks, appears to be selectively induced by three classes of hallucinogens in doses which correlate with those reported to be hallucinogenic in humans. Several non-hallucinogenic congeners of hallucinogens failed to significantly elicit this response. Other behavioral changes induced by hallucinogens in monkeys such as ptosis and social withdrawal may be useful in studying aspects of hallucinogen intoxication other than hallucinations, or psychosis in general. Upon daily administration, tolerance developed to all hallucinogens tested except two, as is seen in humans. Moreover, cross-tolerance between hallucinogens could be demonstrated. Further experiments with the hallucinogen 5-methoxy N,N-dimethyltryptamine revealed that although certain individual behaviors could be antagonized by serotonin antagonists, dopamine antagonists, and physostigmine, no drug completely reversed the behavioral abnormalities induced by this hallucinogen. It is suggested that this paradigm, which offers an hallucinogen-induced behavior which correlates well with the human hallucinogen response and permits observation of a wide variety of other potentially relevant behaviors in primates, may be useful in developing and testing theories of hallucinogenic drug action. It may be especially valuable in view of the present difficulties of conducting hallucinogen research in humans.