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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.

酒精一直被认为是致畸物。然而，人们普遍相信大麻素（CBs）