Experimental and Clinical Psychopharmacology 1996, Vol. 4, No. 1,97-106 Copyright 1996 by the American Psychological Association, Inc. 1064-1297/96/S3.00 Validation of the Multiple-Choice Procedure for Investigating Drug Reinforcement in Humans Roland R. Griffiths, Craig R. Rush, and Kimberly A. Puhala The Johns Hopkins University School of Medicine Three experiments demonstrated the validity of studying drug reinforcement in humans by using a novel Multiple-Choice Procedure. The distinguishing characteristic of the procedure is that it arranges intermittent reinforcement for choices between pairs of potential reinforcers (e.g., drug vs. money). A series of manipulations was conducted, the outcomes of which were predicted on the basis of a well-established literature on operant behavior maintained by food and drug. Specifically, the experiments manipulated reinforcer availability (i.e., extinction), deprivation versus satiation, and reinforcer magnitude in cigarette smokers and demonstrated the predicted changes in cigarette reinforcement as measured by the Multiple-Choice Procedure. Finally, the reinforcer magnitude manipulation was concurrently studied using a conventional two-option choice procedure and the results were shown to be virtually identical to those with the Multiple-Choice Procedure. A variety of procedures for investigating drug reinforcement in humans has been developed and refined over the last two decades (Bigelow, Griffiths, & Liebson, 1975; Griffiths, Big- elow, & Henningfield, 1980; Johanson & de Wit, 1989). These procedures represent variations of drug self-administration methods involving examination of the maintenance of re- peated drug self-administration, choice behavior leading to drug administration, or some combination of the two. A significant limitation of most of the procedures developed to date is that they are relatively time-consuming, often requiring repeated sessions of forced drug exposure or self-administra- tion to generate a single data point. Recently, a highly efficient Multiple-Choice Procedure has been described for investigating drug reinforcement in humans (Griffiths, Troisi, Silverman, & Mumford, 1993). The distin- guishing characteristic of the Multiple-Choice Procedure is that it arranges intermittent reinforcement for choice behav- ior. With this procedure, a participant makes two or more (i.e., multiple) choices on a Multiple-Choice Questionnaire; for each choice, the participant is required to choose one of two Roland R. Griffiths, Department of Psychiatry and Behavioral Sciences and Department of Neuroscience, The Johns Hopkins University School of Medicine; Craig R. Rush and Kimberly A. Puhala, Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine. Craig R. Rush is now at Department of Psychiatry and Human Behavior and Department of Pharmacology and Toxicology, University of Mississippi Medical Center. This project was supported by National Institute on Drug Abuse Research Grants R01-DA-03889 and R01-DA-03890. Correspondence concerning this article should be addressed to Roland R. Griffiths, Department of Psychiatry and Behavioral Sci- ences, Behavioral Biology Research Center, The Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, Maryland 21224. Electronic mail may be sent via Internet to griffiths@bpru.uucp.jhu.edu. potential reinforcers (e.g., drug vs. money choices or drug vs. drug choices). Subsequently, only one of the choices, which is randomly selected, is reinforced (i.e., the choice behavior is consequated). Several studies have used the Multiple-Choice Procedure in assessing the reinforcing effects of orally administered drugs. In a study of pentobarbital in drug abuser participants, the Multiple-Choice Procedure provided a dose-related mea- sure of drug reinforcement that corresponded well with more conventional measures of drug reinforcement such as choice and self-administration (Griffiths et al., 1993). More recently the Multiple-Choice Procedure has been used to evaluate drug reinforcement with alprazolam (Mumford, Rush, & Griffiths, 1995a, 1995b), triazolam (Silverman, Mumford, & Griffiths, 1993), and caffeine (Silverman, Mumford, & Griffiths, 1994), as well as to evaluate the reinforcement value of clinic-based incentives in a methadone-maintenance clinic (e.g., metha- done dose increases; Kidorf, Stitzer, & Griffiths, 1995). Although the Multiple-Choice Procedure appears to pro- vide a useful measure of drug reinforcement, the variables affecting data from the procedure need further experimental analysis. In particular, a more complete characterization of the function of the reinforcement operation in maintaining choice behavior is critical to defining the results from the Multiple- Choice Procedure as reflecting drug reinforcement. To better validate the Multiple-Choice Procedure as a measure of drug reinforcement, we undertook the present set of experiments to assess a series of reinforcer manipulations, the outcomes of which were predicted based on a well-established literature on operant behavior maintained by food and drug (Ferster & Skinner, 1957; Griffiths et al., 1980). Specifically, the experi- ments, which used cigarettes as reinforcers in cigarette smok- ers, manipulated reinforcer availability (i.e., extinction), rein- forcer deprivation versus satiation, and reinforcer magnitude. Also, the reinforcer magnitude manipulation was concurrently studied using a conventional two-option choice procedure to directly compare results with those from the Multiple-Choice Procedure. 97 This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.