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类灵长类动物的临床前研究来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。该提案将通过使用成年恒河猴（雄性和雌性）来解决这个问题，这些恒河猴在怀孕期间在产前暴露于可卡因或生理盐水中；所有猴子现在都至少13岁了。具体目标1将利用涉及食物强化物的延迟折扣程序来评估每只猴子的冲动性。我们假设，在出生前接触可卡因的成年猴子会比对照组更冲动。具体目标2将把这些研究扩展到可卡因的自我给药，包括获取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管理，并且在恢复研究中，将对药物增加反应的能力更加敏感，从而导致生理盐水注射。我们还假设，当任何一种强化物都包含延迟时，出生前暴露于可卡因的猴子会更冲动（即，当替代选择是现在延迟的首选食物时，会选择低剂量的可卡因）。最后，在特异性目标3中，我们将使用正电子发射断层扫描（PET）来检查每只猴子在可卡因自我给药后多巴胺D2受体的可用性。初步的PET数据表明，与对照组相比，在出生前暴露于可卡因的成年猴子中，D2受体的可用性没有差异。我们假设，在自我服用可卡因后，与对照猴子相比，产前暴露于可卡因的猴子D2受体测量值会有更大的减少。这些数据将为产前暴露于可卡因的成年人的行为表型、可卡因滥用易感性和神经可塑性提供有价值的信息。对药物滥用脆弱性的个体差异是人类吸毒成瘾的一个标志。这些研究将进一步探索与药物滥用的病因和维持有关的因素，这将有助于制定新的治疗策略。

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.