Drug Discrimination: Historical Origins, Important Concepts, and Principles.

Abstract

Research on the stimulus properties of drugs began with studies on state dependent learning during the first half of the twentieth century. From that research, an entirely new approach evolved called drug discrimination. Animals (including humans) could discriminate the presence or absence of a drug; once learned, the drug could serve as a discriminative stimulus, signaling the availability or nonavailability of reinforcement. Early drug discrimination research involved the use of a T-maze task, which evolved in the 1970s into a two-lever operant drug discrimination task that is still used today. A number of important concepts and principles of drug discrimination are discussed. (1) The discriminative stimulus properties of drugs are believed in large part to reflect the subjective effects of drugs. While it has been impossible to directly measure subjective effects in nonhuman animals, drug discrimination studies in human subjects have generally supported the belief that discriminative stimulus properties of drugs in nonhuman animals correlate highly with subjective effects of drugs in humans. In addition to the ability of the drug discrimination procedure to measure the subjective effects of drugs, it has a number of other strengths that help make it a valuable preclinical assay. (2) Drug discrimination can be used for classification of drugs based on shared discriminative stimulus properties. (3) The phenomena of tolerance and cross-tolerance can be studied with drug discrimination. (4) Discriminative stimulus properties of drugs typically have been found to be stereospecific, if a drug is comprised of enantiomers. (5) Discriminative stimulus properties of drugs reflect specific CNS activity at neurotransmitter receptors. (6) Both human and nonhuman subjects display individual differences in their sensitivity to discriminative stimuli and drugs. (7) The drug discrimination procedure has been used extensively as a preclinical assay in drug development. This chapter is the first in the volume The Behavioural Neuroscience of Drug Discrimination, which includes chapters concerning the discriminative stimulus properties of various classes of psychoactive drugs as well as sections on the applications and approaches for using this procedure.