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; 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
Czoty, Paul W; Riddick, Natallia V; Gage, H Donald et al. (2009) Effect of menstrual cycle phase on dopamine D2 receptor availability in female cynomolgus monkeys. Neuropsychopharmacology 34:548-54
Riddick, N V; Czoty, P W; Gage, H D et al. (2009) Behavioral and neurobiological characteristics influencing social hierarchy formation in female cynomolgus monkeys. Neuroscience 158:1257-65
Nader, Michael A; Czoty, Paul W (2008) Brain imaging in nonhuman primates: insights into drug addiction. ILAR J 49:89-102
Nader, Michael A; Czoty, Paul W; Gould, Robert W et al. (2008) Review. Positron emission tomography imaging studies of dopamine receptors in primate models of addiction. Philos Trans R Soc Lond B Biol Sci 363:3223-32
Martelle, Jennifer L; Nader, Michael A (2008) A review of the discovery, pharmacological characterization, and behavioral effects of the dopamine D2-like receptor antagonist eticlopride. CNS Neurosci Ther 14:248-62
Sikoski, P; Banks, M L; Gould, R et al. (2007) Comparison of rectal and infrared thermometry for obtaining body temperature in cynomolgus macaques (Macaca fascicularis). J Med Primatol 36:381-4