Drugs can function as positive reinforcers to maintain and strengthen their self-administration and can control behavior through their ability to function as discriminative stimuli. Environmental (e.g., schedule of reinforcement), pharmacological (e.g., mechanism of action) and organismal variables can influence the control of behavior by each of these drug effects. Therefore, the goal of the research described in this RSDA is use animal models to examine the effects of a variety of environmental and pharmacological variables on the reinforcing and discriminative stimulus effects of cocaine. This goal is born of two overarching themes: 1) to increase our knowledge the control of behavior by cocaine, currently a significant problem in the U.S.; 2) to provide basic information that improves our general understanding of the control of behavior by drugs of abuse. Three series of studies are proposed. For the first series, the hypothesis is that drug selfadministration can be reduced by environmental manipulations that alter the reinforcing efficacy of a drug relative to another reinforcer that is simultaneously available. Monkeys will be trained in a discrete-trials choice procedure to choose between an injection of cocaine and a non-drug reinforcer, food. The effect of variables such as the economic system of reinforcer availability, the schedule of reinforcement and punishment on the frequency of drug choice will be determined. The hypothesis of the second series is that cocaine self-administration can be altered by drugs that interact with the neurobiological systems that mediate the reinforcing effect of cocaine. Monkeys will be trained under a multiple schedule of reinforcement with responding maintained at different times by cocaine or food. The ability of various drugs to specifically decrease cocaine self-administration, by either an agonist or antagonist mechanism, will be examined. In addition, we will investigate the interaction of cocaine with other drugs of abuse. The possibility that other drugs of abuse potentiate the reinforcing effect of cocaine when combined with cocaine is relevant to our understanding of poly-drug abuse. A third series will examine pharmacological modification of the discriminative stimulus (DS) effects of cocaine. The rationale and hypothesis are parallel to those of the second series. We will examine the interaction of cocaine with drugs that may alter it's DS effect via a specific neurobiological interaction and the interaction of cocaine with other drugs of abuse. Taken together, these experiments will provide basic information concerning environmental and pharmacological variables that can modify the control of behavior by cocaine. In addition, the information should be generalizable to other drugs of abuse and clinically relevant to the abuse of drugs by humans.
| Ranaldi, Robert; Woolverton, William L (2002) Self-administration of cocaine: scopolamine combinations by rhesus monkeys. Psychopharmacology (Berl) 161:442-8 |
| Woolverton, W L; Hecht, G S; Agoston, G E et al. (2001) Further studies of the reinforcing effects of benztropine analogs in rhesus monkeys. Psychopharmacology (Berl) 154:375-82 |
