According to a 2005 national survey, approximately 4% of pregnant women reported using illicit drugs during pregnancy. As it relates to cocaine, there have been no preclinical studies involving nonhuman primates that assessed the effects of prenatal cocaine exposure on impulsive behavior and vulnerability to cocaine abuse. This proposal will address that issue by using adult rhesus monkeys (male and female) that were prenatally exposed to cocaine or saline throughout gestation;all monkeys are now at least 13 years old.
Specific Aim 1 will utilize delay discounting procedures involving food reinforcers to assess impulsivity in each monkey. We hypothesize that adult monkeys that were prenatally exposed to cocaine will be more impulsive than controls.
Specific Aim 2 will extend these studies to cocaine self-administration, including acquisition and food-cocaine choice. We hypothesize that monkeys that were prenatally exposed to cocaine will acquire cocaine self-administration at lower doses compared to controls and, when studied in reinstatement, will be more sensitive to the ability of drugs to increase responding leading to saline injections. We also hypothesize that when delays are included with either reinforcer, monkeys that were prenatally exposed to cocaine will be more impulsive (i.e., will choose lower doses of cocaine when the alternative is a preferred food that is now delayed). Finally, in Specific Aim 3, we will use positron emission tomography (PET) to examine dopamine D2 receptor availability in each monkey following cocaine self- administration. Preliminary PET data indicated that there were no differences in D2 receptor availability in adult monkeys that were prenatally exposed to cocaine compared to control monkeys. We hypothesize that following cocaine self-administration, monkeys that were prenatally exposed to cocaine will have greater reductions in D2 receptor measures compared to control monkeys. These data will provide valuable information related to behavioral phenotype, vulnerability to cocaine abuse and neural plasticity in adults that were prenatally exposed to cocaine. 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, which should aid in the development of novel treatment strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA025120-05
Application #
8267115
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Lynch, Minda
Project Start
2008-07-01
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2014-05-31
Support Year
5
Fiscal Year
2012
Total Cost
$344,282
Indirect Cost
$111,659
Name
Wake Forest University Health Sciences
Department
Physiology
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
Brutcher, Robert E; Nader, Michael A (2015) Effects of quetiapine treatment on cocaine self-administration and behavioral indices of sleep in adult rhesus monkeys. Psychopharmacology (Berl) 232:411-20
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
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
Brutcher, Robert E; Nader, Michael A (2013) The relationship between cocaine self-administration and actigraphy-based measures of sleep in adult rhesus monkeys. Psychopharmacology (Berl) 229:267-74
Hamilton, Lindsey R; Czoty, Paul W; Nader, Michael A (2011) Behavioral characterization of adult male and female rhesus monkeys exposed to cocaine throughout gestation. Psychopharmacology (Berl) 213:799-808
Gould, Robert W; Gage, H Donald; Banks, Matthew L et al. (2011) Differential effects of cocaine and MDMA self-administration on cortical serotonin transporter availability in monkeys. Neuropharmacology 61:245-51
Hamilton, Lindsey R; Czoty, Paul W; Gage, H Donald et al. (2010) Characterization of the dopamine receptor system in adult rhesus monkeys exposed to cocaine throughout gestation. Psychopharmacology (Berl) 210:481-8