The objectives of this research project are to examine the effects of behavioral history on cocaine self-administration. The behavioral effects of drugs, including reinforcing effects, have been shown to be influenced by behavioral (e.g., schedule of reinforcement) and pharmacological (e.g., drug dose) variables. In addition, a growing body of evidence suggests that factors other than those that currently maintain responding, e.g., an organisms behavioral history, can have profound and long-lasting influences on the rate-altering effects of drugs. However, no data exists regarding modification of the reinforcing effects of drugs by behavioral history. One purpose of the research proposed in the present grant application is to use animal subjects (rhesus monkeys) to examine whether behavioral history can affect the rate and pattern of cocaine-maintained behavior. Subjects will be exposed to schedules of reinforcement that generate high or low rates of responding. Subsequently, rates and patterns of responding will be studied under a fixed-interval (FI) schedule of cocaine presentation. Long-lasting changes in Fl responding as a function of previous schedule of reinforcement will be evidence for an effect of history on drug-maintained behavior. To extend the generality of these findings, other experiments will examine whether a history of responding maintained by a nondrug reinforcer can similarly modify cocaine-maintained responding. A second series of experiments is designed to use a progressive-ratio schedule to examine whether behavioral history can modify the strength of cocaine as a positive reinforcer (i.e., cocaine's reinforcing efficacy). These experiments will examine whether the break point for cocaine (a measure of reinforcing efficacy) can be modified by a behavioral history involving responding for either a drug or nondrug reinforcer under various schedules of reinforcement. Changes in break point as a result of exposure to a particular schedule of reinforcement will be evidence that behavioral history can modify the reinforcing efficacy of cocaine. If the rate and pattern of drug-maintained behavior, as well as the efficacy of a drug as a positive reinforcer, vary with an individual's behavioral history, then knowledge of such historical variables may be important in understanding the etiology, maintenance, treatment and prevention of drug abuse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
1R01DA006829-01
Application #
3213554
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
1991-01-01
Project End
1993-12-31
Budget Start
1991-01-01
Budget End
1991-12-31
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Chicago
Department
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Moore, R J; Vinsant, S L; Nader, M A et al. (1998) Effect of cocaine self-administration on dopamine D2 receptors in rhesus monkeys. Synapse 30:88-96
Nader, M A (1998) The influence of behavioral and pharmacological history on the reinforcing effects of cocaine in rhesus monkeys. NIDA Res Monogr 169:26-55
Moore, R J; Vinsant, S L; Nader, M A et al. (1998) Effect of cocaine self-administration on striatal dopamine D1 receptors in rhesus monkeys. Synapse 28:1-9
Daunais, J B; Nader, M A; Porrino, L J (1997) Long-term cocaine self-administration decreases striatal preproenkephalin mRNA in rhesus monkeys. Pharmacol Biochem Behav 57:471-5
Lyons, D; Friedman, D P; Nader, M A et al. (1996) Cocaine alters cerebral metabolism within the ventral striatum and limbic cortex of monkeys. J Neurosci 16:1230-8
Nader, M A; Mach, R H (1996) Self-administration of the dopamine D3 agonist 7-OH-DPAT in rhesus monkeys is modified by prior cocaine exposure. Psychopharmacology (Berl) 125:13-22
Lamas, X; Negus, S S; Nader, M A et al. (1996) Effects of the putative dopamine D3 receptor agonist 7-OH-DPAT in rhesus monkeys trained to discriminate cocaine from saline. Psychopharmacology (Berl) 124:306-14
Nader, M A; Bowen, C A (1995) Effects of different food-reinforcement histories on cocaine self-administration by rhesus monkeys. Psychopharmacology (Berl) 118:287-94
Nader, M A; Reboussin, D M (1994) The effects of behavioral history on cocaine self-administration by rhesus monkeys. Psychopharmacology (Berl) 115:53-8
Nader, M A; Tatham, T A; Barrett, J E (1992) Behavioral and pharmacological determinants of drug abuse. Ann N Y Acad Sci 654:368-85