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

子宫内可卡因暴露对猴子药物滥用脆弱性的影响。

• 批准号: 8267115
• 负责人: Michael A Nader
• 金额: $ 34.43万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8267115
• 关键词: 13 year old; Abstinence; Address; Administrative Supplement; Adult; Affect; Animals; Behavioral; Brain; Brain imaging; Charge; Cocaine; Cocaine Abuse; Cocaine Dependence; Complement; Data; Development; Dopamine D2 Receptor; Dopamine Receptor; Dose; Drug Addiction; Drug abuse; Etiology; Female; Fetal Cocaine Exposure; Food; Goals; Human; Illicit Drugs; Image; Impulsive Behavior; Impulsivity; Individual; Individual Differences; Injection of therapeutic agent; Laboratories; Lead; Ligands; Macaca mulatta; Maintenance; Measures; Modeling; Monkeys; Mus; Neuronal Plasticity; Pharmaceutical Preparations; Phenotype; Population; Positron-Emission Tomography; Pregnancy; Pregnant Women; Procedures; Psychological reinforcement; Publishing; Rattus; Recording of previous events; Recovery; Relapse; Reporting; Research; Rewards; Saline; Self Administration; Self-Administered; Surveys; Testing; Universities; Work; cocaine exposure; discounting; dopamine system; fluoroclebopride; forest; improved; in utero; male; medical schools; neurochemistry; nonhuman primate; novel; preclinical study; prenatal; prenatal exposure; programs; receptor function; reinforcer; research study; social; trait; treatment strategy

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：根据 2005 年的一项全国调查，大约 4% 的孕妇报告在怀孕期间使用非法药物。由于与可卡因有关，目前还没有涉及非人类灵长类动物的临床前研究评估产前接触可卡因对冲动行为和可卡因滥用脆弱性的影响。该提案将通过使用在怀孕期间在产前接触可卡因或盐水的成年恒河猴（雄性和雌性）来解决这个问题；所有猴子现在都至少 13 岁。具体目标 1 将利用涉及食物强化剂的延迟贴现程序来评估每只猴子的冲动性。我们假设，出生前接触可卡因的成年猴子会比对照组更容易冲动。具体目标 2 将把这些研究扩展到可卡因自我给药，包括获取和食物可卡因选择。我们假设，与对照组相比，产前接触可卡因的猴子会以较低剂量进行可卡因自我给药，并且在恢复研究时，会对药物增加导致盐水注射的反应的能力更加敏感。我们还假设，当任何一种强化剂都包含延迟时，产前接触可卡因的猴子会更加冲动（即，当替代品是现在延迟的首选食物时，会选择较低剂量的可卡因）。最后，在具体目标 3 中，我们将使用正电子发射断层扫描 (PET) 来检查每只猴子自我施用可卡因后多巴胺 D2 受体的可用性。初步 PET 数据表明，与对照猴相比，产前接触可卡因的成年猴的 D2 受体可用性没有差异。我们假设，在自我给予可卡因后，与对照猴相比，产前接触可卡因的猴子的 D2 受体测量值会出现更大程度的减少。这些数据将提供与行为表型、可卡因滥用脆弱性以及产前接触可卡因的成年人的神经可塑性相关的有价值的信息。药物滥用脆弱性的个体差异是人类药物成瘾的标志。这些研究将进一步探讨与药物滥用的病因和维持相关的因素，这将有助于开发新的治疗策略。