The overarching goal of this research is to achieve a better understanding of the individual differences in the susceptibility and vulnerability to the reinforcing effects of cocaine using a unique nonhuman primate model of drug abuse. To accomplish this, we have combined the study of primate social behavior with intravenous drug self-administration and the noninvasive brain imaging procedure positron emission tomography (PET) to examine how environmental and pharmacological variables influence the behavioral and reinforcing effects of cocaine. In the previous funding period we found that social housing altered dopamine (DA) D2 receptor function in male cynomolgus monkeys and these changes were associated with differential vulnerability to self-administer cocaine between dominant and subordinate monkeys. These studies were the first to examine intravenous cocaine self-administration in socially housed monkeys and found that social status and environmental context can have profound effects on cocaine reinforcement. We also found that chronic exposure to cocaine could attenuate the effects of social rank on DA receptor function and result in similar rates of self-administration among the socially housed monkeys. The studies proposed in this competing renewal application are designed to evaluate further the interactions between DA, social rank and the reinforcing effects of cocaine. Specifically, we propose to 1) examine further the plasticity of the DA system during cocaine abstinence and following social group reorganization and assess the impact of these manipulations on cocaine reinforcement;2) determine the effects of social consequences of self-administering cocaine on the reinforcing effects of the drug and on measures of impulsivity;and 3) examine further the interactions between acute and chronic environmental stressors and enrichment on DA receptor function and on the reinforcing effects of cocaine, as a function of social rank. The use of novel and homologous nonhuman primate models of cocaine abuse, as proposed, should aid in understanding how environmental and pharmacological variables contribute to vulnerability, maintenance, relapse and choice behavior involving drugs of abuse. Such information will lead to better treatment and prevention strategies.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Method to Extend Research in Time (MERIT) Award (R37)
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Special Emphasis Panel (ZRG1-IFCN-A (07))
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Lynch, Minda
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Wake Forest University Health Sciences
Schools of Medicine
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John, William S; Nader, Michael A (2017) Effects of ethanol on cocaine self-administration in monkeys responding under a second-order schedule of reinforcement. Drug Alcohol Depend 170:112-119
Heilig, Markus; Epstein, David H; Nader, Michael A et al. (2016) Time to connect: bringing social context into addiction neuroscience. Nat Rev Neurosci 17:592-9
Nader, Michael A (2016) Animal models for addiction medicine: From vulnerable phenotypes to addicted individuals. Prog Brain Res 224:3-24
Czoty, Paul W; Stoops, William W; Rush, Craig R (2016) Evaluation of the ""Pipeline"" for Development of Medications for Cocaine Use Disorder: A Review of Translational Preclinical, Human Laboratory, and Clinical Trial Research. Pharmacol Rev 68:533-62
Maldjian, Joseph A; Shively, Carol A; Nader, Michael A et al. (2016) Multi-Atlas Library for Eliminating Normalization Failures in Non-Human Primates. Neuroinformatics 14:183-90
Czoty, Paul W; Nader, Michael A (2015) Effects of oral and intravenous administration of buspirone on food-cocaine choice in socially housed male cynomolgus monkeys. Neuropsychopharmacology 40:1072-83
Kromrey, Sarah A; Gould, Robert W; Nader, Michael A et al. (2015) Effects of prior cocaine self-administration on cognitive performance in female cynomolgus monkeys. Psychopharmacology (Berl) 232:2007-16
Kromrey, Sarah A; Czoty, Paul W; Nader, Michael A (2015) Relationship between estradiol and progesterone concentrations and cognitive performance in normally cycling female cynomolgus monkeys. Horm Behav 72:12-9
Keck, Thomas M; John, William S; Czoty, Paul W et al. (2015) Identifying Medication Targets for Psychostimulant Addiction: Unraveling the Dopamine D3 Receptor Hypothesis. J Med Chem 58:5361-80
Nader, Michael A; Banks, Matthew L (2014) Environmental modulation of drug taking: Nonhuman primate models of cocaine abuse and PET neuroimaging. Neuropharmacology 76 Pt B:510-7

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