Serotonergic receptor subtypes and hallucinogen-induced stimulus control

More than a quarter century has passed since the demonstration that indolea mine and phenethylamine hallucinogens can function as discriminative stimul i in the rat, and that serotonergic systems are critically involved. During that period our knowledge of the physiology, pharmacology, biochemistry, a nd molecular biology of serotonergic receptors has increased exponentially; with each advance it has been necessary to reexamine our assumptions regar ding hallucinogen-induced stimulus control. Of particular interest is the h ypothesis that a drug may act, at a molecular level, upon multiple receptor s to produce, at a behavioral level, a compound discriminative stimulus. Th e salience of the individual elements of such compound stimuli may be influ enced by a variety of experimental factors including training dose, pretrea tment time, the state of sensitization of the systems being acted upon, and the nature of the drugs chosen for tests of generalization. This article p rovides examples of experimental approaches to these complexities using sel ective agonists and antagonists, depletion-induced sensitization, and antag onist correlation analysis. (C) 1999 Elsevier Science Inc.