Winger, G. Abstract Two behavioral economic concepts have been described as related to human drug abuser: inability to delay gratification as indicated by a relatively high choice for small immediate reinforcers over delayed, larger reinforcers, and relatively inelasitc demand for the drug itself. Work in our laboratory with nonhuman primates has revealed that drugs with substantial abuse liability (e.g., cocaine or mu- opioid agonists) produce demand curves with less elasticity of demand than drugs with reduced abuse liability (e.g., ketamine or short-acting barbiturates). More recently, we have found marked individual differences among monkeys with respect to economic demand for various drugs of abuse. Furthermore monkeys that have a high demand for one drug are very likely to have high demand for all other tested drugs, suggesting that some monkeys may be more like human drug abusers, and other monkeys are more resistant to the reinforcing effects of drugs. We have begun to measure impulsivity in rhesus monkeys as well, using remifentanil, and to a lesser extent, food as the reinforcers. Evidence for an impulsivity trait is less clear than is the evidence for a """"""""demand"""""""" trait. Nevertheless, there is a trend toward a significant correlation between high demand and high impulsivity in individual monkeys. In the present proposal, we propose to continue to investigate this possible relationship between a measure of drug abuse, and a measure of impulsivity. In addition, we propose to use monkeys that differ in their early-life rearing;specifically, the monkeys were raised either by their mothers, or in a nursery with peers of a similar age. Peer-rearing has been shown to result in an increased response to stressors and greater propensity to self-administer ethanol in previous studies, and we will determine if this correlates with impulsivity and/ or demand for drug. These experiments will help to evaluate the premise that impulsivity is trait that is genetically determined and/or established by a particular environment early in life. Understanding more about the cause-and-effect relation between drug abuse and impulsivity could assist in devising strategies for reducing impulsivity that could be adjuncts to drug treatment intervention and drug-use prevention programs.

Public Health Relevance

This research is designed to evaluate in non-human primates whether impulsivity is a trait variable, whether it is influenced by early environment, and is related to vulnerability to drug abuse. This information will be useful in answering the question of whether impulsivity leads to drug abuse or drug abuse leads to impulsivity. This in turn will help clinicians and clinical investigators devise appropriate adjuncts to drug abuse intervention and treatment strategies based on modification of impulsive behavior.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Special Emphasis Panel (ZRG1-BBBP-T (03))
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Lynch, Minda
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University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
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Koffarnus, Mikhail N; Winger, Gail (2015) Individual differences in the reinforcing and punishing effects of nicotine in rhesus monkeys. Psychopharmacology (Berl) 232:2393-403
Lagorio, Carla H; Winger, Gail (2014) Random-ratio schedules produce greater demand for i.v. drug administration than fixed-ratio schedules in rhesus monkeys. Psychopharmacology (Berl) 231:2981-8
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
Koffarnus, Mikhail N; Hall, Amy; Winger, Gail (2012) Individual differences in rhesus monkeys' demand for drugs of abuse. Addict Biol 17:887-96
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
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