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

基本信息

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
项目类别：
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

项目摘要

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.

酒精长期以来被认为是一种致畸剂。然而，人们普遍认为大麻素（CB）为了怀孕期间的安全。产前接触大麻和动物的儿童的行为观察 THC 和最近推出的高效合成大麻素 (SCB) 的研究与此相矛盾相信并表明接触大麻素确实会致畸。重要的是，在啮齿类动物中，产前早期接触 SCB 会导致类似于胎儿酒精综合症的出生缺陷。怀孕初期，双方酒精和大麻素独立诱发涉及腹侧中线衍生结构的大脑异常，包括下丘脑、间隔区和纹状体。我们假设这两种药物在服用时在原肠胚形成和神经形成的早期阶段一起，将具有显着的持续致畸作用对新奇/习惯过程的反应改变、皮质酮反应和酒精所证明的效果青少年后代的自我管理。使用关键时期产前致畸剂暴露的大鼠模型原肠胚形成和神经形成的发育事件，拟议的研究将探讨这个前提，解决以下具体目标：目标 1 将检查产前酒精+SCB 暴露对运动活动和对新环境的适应，以及皮质酮对轻微反应的变化压力源。目标 2 将检验以下假设：妊娠早期酒精+SCB 暴露会增强酒精自噬管理、自我饮酒的动机和饮酒行为。这些数据将很重要有关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。