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Impact of In Utero Cocaine Exposure on Vulnerability to Drug Abuse in Monkeys.

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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.
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