Drug abuse continues to be a major public health problem worldwide, with an estimated 1.6 million Americans confirming current cocaine use. There is evidence of sex differences in vulnerability to cocaine abuse, although males are disproportionately represented in research. This research project is a continuation of funded work aimed at understanding the neurobiology of cocaine abuse in a unique nonhuman primate model: intravenous cocaine self-administration in socially housed female monkeys. We have successfully 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.
Specific Aim 1 will examine the effects of chronic cocaine self-administration on dopamine (DA) D2/D3 receptors and DA transporters (DAT), brain systems that have been well characterized in males, but not females.
Specific Aim 2 will examine whether acute social stress differentially affects cocaine self- administration as a function of social rank and whether dominant and subordinate females respond similarly to chronic drug treatment. Finally, in Specific Aim 3, we will combine environmental enrichment and chronic drug treatment in an effort to decrease the reinforcing strength of cocaine in dominant and subordinate monkeys. We hypothesize individual differences, based on social rank-induced differences in D2/D3 and DAT availability, in response to environmental challenges and drug treatments. The combination of social rank and PET imaging studied over years, in female monkeys, will allow for a better understanding of the interactions between social context and DA receptor function, which will be critical to developing behavioral and pharmacological treatment strategies.

Public Health Relevance

Individual differences in vulnerability to drug abuse is a hallmark of human drug addiction. These studies will further explore factors related to etiology and maintenance of drug abuse in socially housed female monkeys, which should aid in the development of novel treatment strategies.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
3R01DA017763-08S1
Application #
8892623
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Lynch, Minda
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Physiology
Type
Schools of Medicine
DUNS #
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
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
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
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
Nader, Michael A; Balster, Robert L; Henningfield, Jack E (2014) William L. Woolverton: a case history in unraveling the behavioral pharmacology of stimulants. Neuropharmacology 87:4-8
Gould, Robert W; Duke, Angela N; Nader, Michael A (2014) PET studies in nonhuman primate models of cocaine abuse: translational research related to vulnerability and neuroadaptations. Neuropharmacology 84:138-51
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
Gould, Robert W; Porrino, Linda J; Nader, Michael A (2012) Nonhuman primate models of addiction and PET imaging: dopamine system dysregulation. Curr Top Behav Neurosci 11:25-44
Nader, Michael A; Czoty, Paul W; Nader, Susan H et al. (2012) Nonhuman primate models of social behavior and cocaine abuse. Psychopharmacology (Berl) 224:57-67
Nader, Michael A; Nader, Susan H; Czoty, Paul W et al. (2012) Social dominance in female monkeys: dopamine receptor function and cocaine reinforcement. Biol Psychiatry 72:414-21

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