Animal Models for Assessing Hallucinogenic Agents

Hallucinogenic activity, by definition, can be measured only in human subjects. Nevertheless, there may be an animal counterpart, or a behavioral or physiological response that parallels hallucinogenic activity/potency in humans and will be a useful predictor of hallucinogenic potential or abuse liability. Over the years, a variety of tests or models have been explored for the purpose of identifying such agents. Although some of these models have contributed enormously to our understanding of hallucinogenic agents, their mechanism of action, and their structure-activity relationships, a single, all-purpose, reliable animal model remains elusive. The situation is rooted in problems that only now are becoming understood—for example, the confusion associated with the classification of hallucinogenic substances, and the lack of a “pure” prototypic hallucinogen. Is it appropriate to lump together in a single class all agents capable of producing a psychotomimetic response? Exactly what constitutes a hallucinogenic/psychotomimetic response in humans? Humans can differentiate the effects of different hallucinogenic agents; some of these differentiating effects may be of a central origin, whereas others may be peripheral in nature.