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

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。由于它与可卡因有关，目前还没有涉及非人灵长类动物的临床前研究，评估产前可卡因暴露对冲动行为和可卡因滥用脆弱性的影响。这项提案将通过使用在整个妊娠期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将利用涉及食品加工商的延迟折扣程序评估每只猴的冲动性。我们假设，出生前接触可卡因的成年猴子比对照组更冲动。具体目标2将这些研究扩展到可卡因自我管理，包括收购和食物可卡因的选择。我们假设，与对照组相比，产前暴露于可卡因的猴子将获得较低剂量的可卡因自我给药，并且在恢复研究时，对药物增加生理盐水注射反应的能力更敏感。我们还假设，当任何一种可卡因都包括延迟时，产前暴露于可卡因的猴子会更冲动（即，当替代品是现在被推迟的首选食物时，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）检查可卡因自我给药后每只猴的多巴胺D2受体可用性。初步PET数据表明，与对照组猴子相比，产前暴露于可卡因的成年猴子的D2受体可用性没有差异。我们假设，可卡因自我管理后，猴子产前暴露于可卡因将有更大的减少D2受体的措施相比，控制猴子。这些数据将提供有价值的信息，行为表型，可卡因滥用的脆弱性和神经可塑性的成年人产前暴露于可卡因。药物滥用易感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。

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.