Is addiction accompanied by an increase in the absolute reinforcing effect of a drug or the relative reinforcing effect of a drug, or both? The new research described in this proposal will attempt to answer this question in a search for substantive behavioral changes that occur as a function of chronic drug administration. The research will build on previous studies using intravenous drug self-administration in rhesus monkeys and behavioral economic evaluation of reinforcing effectiveness using demand curve elasticity measures. Demand for remifentanil or cocaine will be evaluated when the drugs are available for limited periods of time each day, and then when access to an opioid or a stimulant is increased to as much as two hours out of every six hours around the clock. Relative reinforcing effectiveness will be evaluated in studies where the monkeys can choose between drug and food under similar conditions of 2, 4, 6, and 8 hours per day of intermittent access to drug. Past research has demonstrated that monkeys increasingly choose remifentanil over cocaine in the presence of morphine withdrawal, and some animals show increased demand for both drugs during morphine withdrawal. Parallel studies will evaluate the effect of chronic administration of amphetamine on choice of remifentanil and cocaine under similar conditions of intoxication and withdrawal. It is hoped that a better understanding of the behavioral implications of chronic drug administration will assist in defining and quantifying addiction, and that this will serve as a touchstone for work designed to understand social and physiological correlates of addiction as well as behavioral and pharmacological interventions that are designed to reduce this excessive and destructive behavior.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA015449-07
Application #
7660481
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Wetherington, Cora Lee
Project Start
2002-07-01
Project End
2011-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
7
Fiscal Year
2009
Total Cost
$450,902
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Pharmacology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Koffarnus, Mikhail N; Woods, James H (2013) Individual differences in discount rate are associated with demand for self-administered cocaine, but not sucrose. Addict Biol 18:8-18
Koffarnus, Mikhail N; Hall, Amy; Winger, Gail (2012) Individual differences in rhesus monkeys' demand for drugs of abuse. Addict Biol 17:887-96
Koffarnus, Mikhail N; Collins, Gregory T; Rice, Kenner C et al. (2012) Self-administration of agonists selective for dopamine D2, D3, and D4 receptors by rhesus monkeys. Behav Pharmacol 23:331-8
Jimenez-Gomez, Corina; Winger, Gail; Dean, Reginald L et al. (2011) Naltrexone decreases D-amphetamine and ethanol self-administration in rhesus monkeys. Behav Pharmacol 22:87-90
Podlesnik, Christopher A; Ko, Mei-Chuan; Winger, Gail et al. (2011) The effects of nociceptin/orphanin FQ receptor agonist Ro 64-6198 and diazepam on antinociception and remifentanil self-administration in rhesus monkeys. Psychopharmacology (Berl) 213:53-60
Wade-Galuska, Tammy; Galuska, Chad M; Winger, Gail (2011) Effects of daily morphine administration and deprivation on choice and demand for remifentanil and cocaine in rhesus monkeys. J Exp Anal Behav 95:75-89
Koffarnus, Mikhail N; Newman, Amy H; Grundt, Peter et al. (2011) Effects of selective dopaminergic compounds on a delay-discounting task. Behav Pharmacol 22:300-11
Ko, Mei-Chuan; Woods, James H; Fantegrossi, William E et al. (2009) Behavioral effects of a synthetic agonist selective for nociceptin/orphanin FQ peptide receptors in monkeys. Neuropsychopharmacology 34:2088-96
Koffarnus, Mikhail N; Woods, James H (2008) Quantification of drug choice with the generalized matching law in rhesus monkeys. J Exp Anal Behav 89:209-24
Hursh, Steven R; Silberberg, Alan (2008) Economic demand and essential value. Psychol Rev 115:186-98

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