Since drugs are usually available to humans simultaneously with other reinforcers, an understanding of factors that control choice between drugs and other drug or non-drug reinforcers is important to a complete understanding drug abuse. Indeed, the behavioral transition to virtually exclusive choice of drug over other reinforcers could be considered the defining feature of drug abuse. The experiments described in the present proposal will utilize an animal model of drug abuse, i.v. self-administration by monkeys, to examine behavioral and pharmacological variables that control drug choice. By understanding these variables, we hope to enhance our understanding of factors that determine the transition to uncontrolled drug use. The research should contribute important basic information to the development of novel approaches to the treatment of drug abuse. The research has three Specific Aims, each framed in the context of a model that generally predicts choice for reinforcers other than drugs.
Specific Aim 1 is to investigate the interaction between reinforcer magnitude and frequency as determinants of drug choice. Results will be compared to predictions of the matching law, that organisms will apportion behavior according to relative magnitudes of reinforcement.
Specific Aim 2 is to investigate delay of reinforcement as a controlling variable in drug choice. Results will be compared to predictions of the hyperbolic delay discounting model and models of """"""""impulsivity"""""""" and """"""""self-control."""""""" Since most drug abusers have a choice between drug and non-drug reinforcers, Specific Aim 3 is to investigate the nature of the alternative reinforcer to drug as a controlling variable in choice.Behavioral economics predicts that choice is controlled by the relative substitutability of alternative reinforcers that are available. The experiments in each Specific Aim will examine representatives of two classes of abused drugs, psychomotor stimulants (cocaine) and opioids (alfentanil). In addition, to examine the generality of our conclusions to behavior maintained by non-drug reinforcers, we will study behavior maintained by food. The proposed research will help elucidate the drug-organism-environment interaction that determines drug abuse, and may provide a laboratory model of uncontrolled drug use. From the point of view of basic behavioral research, the research will expand our understanding of choice in general. Theories of choice should accommodate drug choice as well as choice involving non-drug reinforcers. Further, an understanding of the variables that control the choice to self-administer a drug is crucial to the refinement of drug abuse treatment.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Special Emphasis Panel (ZRG1-BBBP-1 (01))
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Wetherington, Cora Lee
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University of Mississippi Medical Center
Schools of Medicine
United States
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Freeman, Kevin B; Green, Leonard; Myerson, Joel et al. (2009) Delay discounting of saccharin in rhesus monkeys. Behav Processes 82:214-8
Woolverton, William L; Myerson, Joel; Green, Leonard (2007) Delay discounting of cocaine by rhesus monkeys. Exp Clin Psychopharmacol 15:238-44
Woolverton, William L; Anderson, Karen G (2006) Effects of delay to reinforcement on the choice between cocaine and food in rhesus monkeys. Psychopharmacology (Berl) 186:99-106
Anderson, Karen G; Woolverton, William L (2004) Dose and schedule determinants of cocaine choice under concurrent variable-interval schedules in rhesus monkeys. Psychopharmacology (Berl) 176:274-80
Anderson, Karen G; Woolverton, William L (2003) Effects of dose and infusion delay on cocaine self-administration choice in rhesus monkeys. Psychopharmacology (Berl) 167:424-30
Anderson, Karen G; Velkey, Andrew J; Woolverton, William L (2002) The generalized matching law as a predictor of choice between cocaine and food in rhesus monkeys. Psychopharmacology (Berl) 163:319-26
Anderson, K G; Woolverton, W L (2000) Concurrent variable-interval drug self-administration and the generalized matching law: a drug-class comparison. Behav Pharmacol 11:413-20
Woolverton, W L; Alling, K (1999) Choice under concurrent VI schedules: comparison of behavior maintained by cocaine or food. Psychopharmacology (Berl) 141:47-56
Woolverton, W L; Rowlett, J K (1998) Choice maintained by cocaine or food in monkeys: effects of varying probability of reinforcement. Psychopharmacology (Berl) 138:102-6
Woolverton, W L; English, J A; Weed, M R (1997) Choice between cocaine and food in a discrete-trials procedure in monkeys: a unit price analysis. Psychopharmacology (Berl) 133:269-74

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