Consequences of prenatal alcohol and cannabinoid co-exposure on alcohol self-administration in adolescence

产前酒精和大麻素共同暴露对青春期自我饮酒的影响

• 批准号: 9763396
• 负责人: JOYCE BESHEER
• 金额: $ 7.78万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9763396
• 关键词: Address; Adolescence; Adolescent; Adolescent Behavior; Alcohol consumption; Alcohols; Animals; Behavioral; Belief; Brain; Cannabinoids; Child; Congenital Abnormality; Corpus striatum structure; Corticosterone; Cues; Data; Development; Dose; Drug usage; Embryo; Environment; Event; Exposure to; Extinction (Psychology); Face; Fetal Alcohol Syndrome; Fetal alcohol effects; Goals; Hypothalamic structure; Knowledge; Maintenance; Marijuana; Modeling; Motivation; Motor Activity; Pharmaceutical Preparations; Predisposition; Pregnancy; Process; Rattus; Research; Rodent; Schedule; Self Administration; Septal Area; Sex Differences; Structure; Techniques; Teratogenic effects; Teratogens; Testing; adolescent offspring; alcohol effect; alcohol seeking behavior; behavior observation; brain abnormalities; design; dosage; drinking behavior; experimental study; fetal drug exposure; gastrulation; habituation; high risk drinking; neurobehavioral; novel; prenatal; prenatal exposure; response; stressor; synthetic cannabinoid; underage drinking

Alcohol has long been recognized as a teratogen. Cannabinoids (CBs), however, have been popularly believed to be safe during pregnancy. Behavioral observations in children prenatally exposed to marijuana, and animal studies of THC and the more recently introduced, highly potent synthetic cannabinoids (SCBs), contradict this belief and indicate that cannabinoid exposure is, indeed, teratogenic. Importantly, in rodents, early prenatal exposure to SCBs causes birth defects similar to those in fetal alcohol syndrome. During early gestation, both alcohol and cannabinoids independently induce brain abnormalities involving ventral midline-derived structures, including the hypothalamus, septal area and striatum. We hypothesize that these two drugs, when administered together during the early periods of gastrulation and neurulation, will have a significant persistent teratogenic effect as evidenced by altered response to novelty/habituation processes, corticosterone responses and alcohol self-administration in adolescent offspring. Using a rat model of prenatal teratogen exposure during the key developmental events of gastrulation and neurulation, the proposed research will explore this premise, addressing the following Specific Aims: Aim 1 will examine the effect of prenatal alcohol+SCB exposure on locomotor activity and habituation to a novel environment, and changes in corticosterone in response to a mild stressor. Aim 2 will test the hypothesis that early gestational alcohol+SCB exposure will potentiate alcohol self- administration, motivation to self-administer alcohol and alcohol-seeking behavior. These data will be important information on the functional effects of prenatal co-exposure to two widely used drugs and how this may increase adolescent drinking behaviors.

长期以来，酒精被认为是一种致畸剂。然而，人们普遍认为大麻素（CB） 在怀孕期间保持安全。产前接触大麻和动物的儿童的行为观察 对THC和最近引入的高效合成大麻素（SCBs）的研究与此相矛盾 相信并表明大麻素暴露确实是致畸的。重要的是，在啮齿动物中， 暴露于SCB会导致与胎儿酒精综合征相似的出生缺陷。在妊娠早期， 酒精和大麻素独立地诱导涉及腹侧中线衍生结构的脑异常， 包括下丘脑隔区和纹状体我们假设这两种药物， 在原肠胚形成和神经胚形成的早期， 通过对新奇/习惯化过程的反应改变、皮质酮反应和酒精证明的效应 青少年后代的自我管理。使用大鼠模型的产前致畸剂暴露期间的关键 原肠胚形成和神经胚形成的发育事件，拟议的研究将探讨这一前提， 解决以下具体目标：目标1将检查产前酒精+SCB暴露对 运动活动和适应新环境，以及皮质酮对轻度 压力源目的2将检验妊娠早期酒精+SCB暴露将增强酒精自我保护的假设。 管理，自我管理酒精和酒精寻求行为的动机。这些数据将是重要的 关于产前同时接触两种广泛使用的药物的功能影响以及这种影响如何增加的信息 青少年饮酒行为