Drug Discrimination

The psychoactive effect of a drug usually refers to a chemical agent that exerts an action upon the central nervous system (CNS), alters brain function, and, consequently, produces a temporary change in an individual’s mood, feelings, perception, and/or behavior. Such agents may be prescribed as therapeutic medications or used (or abused) as recreational drugs. In each case, the subjective effects produced by such agents are generally not accessible to independent verification by an observer. However, methods were developed about 50 years ago whereby human subjects could self-rate their experiences on questionnaires after administration of a drug [1]. Generally, these self-inventories require subjects to provide information about themselves and are considered valuable because they venture “below the surface” to glean the effect of a drug on an individual. Also, they are convenient because they (usually) do not require the services of a group of raters or interviewers. Their chief disadvantage may be that individuals might not completely understand the effect of the drug or their drug “experience” and therefore might not always give an accurate report. The drug discrimination (DD) paradigm is an assay of, and relates to, the subjective effect of drugs in nonhuman animals or humans. In a typical DD experiment, there are four basic components: (1) the subject, (2) the dose of drug that exerts an effect on the subject and precedes a response by the subject, (3) an appropriate (or correct) response, and (4) presentation of reinforcement. SUBJECT → DOSE OF DRUG → RESPONSE → REINFORCEMENT The drug effect that “leads to” a behavioral event (i.e., particular response) and signals that reinforcement is available is called the discriminative stimulus. A wide variety of psychoactive drugs can serve as discriminative stimuli (see below). In laboratory subjects, discriminative control by (usually) two treatments is established through the use of reinforcement (reward). When subjects receive a dose of a drug, it functions as a signal that prompts a correct behavioral response and results in the presentation of a reward. In other words, the effect of the drug is used as a “help” or “aid” to control appropriate behavioral responding by signaling that reinforcement is (or will be) available. Subjects are usually trained to distinguish administration of a particular dose of a particular drug (i.e., the training dose of a training drug) from administration of saline vehicle (i.e., usually a 0.9% sodium chloride solution that is often used as a solvent for many parenterally administered drugs). In a subject’s course of training sessions, the dose of drug is administered (i.e., drug sessions) and lever presses on the drug-designated lever (for that subject) produce reinforcement. In other training sessions, saline is administered (i.e., vehicle sessions) and responses on the (alternate) saline-designated lever produce reinforcement. The DD procedure can be characterized as a highly sensitive and very specific drug detection method that provides both quantitative and qualitative data on the effect of a training drug in relation to the effect of a test (i.e., challenge) agent. Historically, DD studies are linked by a common requirement that subjects must perform an appropriate (or correct) response that indicates a distinction was made between drug and nondrug conditions. As such, when employed with animals or humans, a subject’s response permits an experimenter to determine if a drug effect has been “perceived.” An excellent source of information on DD studies can be found at the Drug Discrimination Bibliography Web site (http://www.dd-database.org). The Web site, established and maintained by Drs. Ian P. Stolerman and Jonathan B. Kamien, is funded by the National Institute on Drug Abuse (NIDA) of the National Institutes of Health (NIH) and contains close to 4000 DD references published between 1951 and the present. The citations include DD abstracts, journal articles, reviews, book chapters, and books. In addition, the Web site can be navigated to selectively retrieve references on particular training drugs, drug classes, test drugs, authors, and DD methodologies.