Binge Cocaine During Pregnancy in the Rat

老鼠怀孕期间暴饮可卡因

• 批准号: 7835611
• 负责人: DIANA L DOW-EDWARDS
• 金额: $ 19.85万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-15 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7835611
• 关键词: Abstinence; Address; Affect; Animal Model; Behavior; Blood; Brain; Brain region; Child; Chronic; Cocaine; Cocaine Abuse; Corpus striatum structure; Crack Cocaine; Data; Development; Dopamine; Dose; Drug Kinetics; Fetal Cocaine Exposure; Future; Human; Individual; Intravenous; Investigation; Life; Literature; Metabolic Clearance Rate; Modeling; Pattern; Perinatal Exposure; Pharmaceutical Preparations; Pregnancy; Psychological reinforcement; Rattus; Rewards; Rodent; Rodent Model; Route; Smoke; Smoker; Smoking; Staging; System; base; cocaine exposure; cocaine use; exposed human population; extracellular; fetal; neurobehavioral; pre-clinical; pregnant; prenatal; public health relevance

DESCRIPTION (provided by applicant): In spite of 20 years of investigations of the effects of prenatal cocaine exposure in rodents, no one has modeled the binge pattern associated with smoking crack/cocaine in a pregnant rat. Cocaine use has gone down nationwide, but there remains a substantial number of individuals who have been exposed to crack/cocaine during prenatal life and the question remains, are the neurobehavioral alterations greater or perhaps less than those who have been exposed by other routes of administration? Crack smokers smoke repeatedly in a single binge. The rapidly increasing and decreasing blood/brain levels of cocaine as produced by smoking crack result in the greatest "reinforcement" to the smoker and presumably result in parallel fetal exposure. The effects of these rapidly increasing and decreasing cocaine levels during gestation are for the most part unknown. Aim 1 of this application will establish a binge model of crack/cocaine abuse during pregnancy in the rat using an indwelling jugular port and repeated rapid intravenous dosing. Aim 2 will determine peak and clearance of cocaine and metabolites in blood and brain to facilitate a comparison with maternal and fetal exposures of human crack smokers. Also, this aim will determine whether a single cocaine binge will result in detectable fetal cocaine and metabolite levels. Together, these studies will develop a translational model of crack smoking during pregnancy to set the stage for future studies especially on the effects of binge cocaine exposure on the development of reward systems known to be affected by the binge pattern of cocaine administration. PUBLIC HEALTH RELEVANCE: This application will develop a rat model of crack/cocaine bingeing during pregnancy in humans. We will utilize indwelling jugular ports to administer cocaine binges IV both before and during pregnancy in the rat since IV closely approximates the pharmacokinetics of smoking crack. Additionally, we will assess the blood and brain levels of cocaine and metabolites resulting from chronic bingeing to enable comparisons with human exposures.

描述（由申请人提供）：尽管对啮齿动物产前接触可卡因的影响进行了 20 年的研究，但没有人模拟怀孕大鼠与吸食可卡因/可卡因相关的暴食模式。全国范围内可卡因的使用量已经下降，但仍有相当多的人在产前接触过可卡因/可卡因，问题仍然存在，神经行为的改变是否比那些通过其他给药途径接触过的人更大或可能更少？吸毒者在一次暴饮暴食中反复吸烟。吸食快克产生的血液/大脑中可卡因水平迅速增加和减少，对吸烟者产生最大的“强化”，并可能导致胎儿平行暴露。妊娠期间可卡因水平快速增加和减少的影响在很大程度上是未知的。本申请的目标 1 将使用留置颈静脉端口和重复快速静脉注射给药，建立大鼠妊娠期间可卡因/可卡因滥用的暴饮暴食模型。目标 2 将确定血液和大脑中可卡因和代谢物的峰值和清除率，以便于与人类吸毒者的母亲和胎儿暴露情况进行比较。此外，这一目标还将确定单次可卡因狂欢是否会导致可检测到的胎儿可卡因和代谢物水平。这些研究将共同​​开发怀孕期间吸毒的转化模型，为未来的研究奠定基础，特别是关于暴饮可卡因暴露对已知受可卡因给药模式影响的奖励系统发育的影响。公共健康相关性：该应用程序将开发人类怀孕期间暴饮可卡因/可卡因的大鼠模型。我们将利用留置颈静脉端口在大鼠怀孕前和怀孕期间对可卡因进行静脉注射，因为静脉注射与吸食可卡因的药代动力学非常接近。此外，我们将评估长期暴饮造成的可卡因和代谢物的血液和大脑水平，以便与人类暴露量进行比较。