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

长期以来，酒精一直被认为是一种致畸剂。然而，人们普遍认为大麻素(CBS) 在怀孕期间是安全的。产前接触大麻的儿童和动物的行为观察 对THC和最近引入的高效合成大麻素(SCB)的研究与此相矛盾 我们相信，并表明暴露于大麻类物质确实具有致畸性。重要的是，在啮齿类动物中，产前早期 暴露于SCBS会导致类似于胎儿酒精综合症的出生缺陷。在怀孕早期，两者 酒精和大麻素独立地诱导涉及腹中线派生结构的大脑异常， 包括下丘脑、隔区和纹状体。我们假设这两种药物在给药时 在原肠形成和神经形成的早期阶段，会有显著的持久致畸作用 通过对新奇/习惯化过程、皮质酮反应和酒精反应的改变而证明的效果 青春期子女的自我管理。采用胎儿期暴露致畸物质的大鼠模型 原肠和神经形成的发育事件，拟议的研究将探索这一前提， 针对以下具体目标：目标1将研究产前酒精对母体健康的影响 运动活动和对新环境的习惯化，以及皮质酮对轻度刺激的反应变化 压力源。目的2将检验这一假说，即妊娠早期接触酒精会增强酒精自身 管理、自我管理酒精的动机和寻酒行为。这些数据将是重要的 关于产前共同接触两种广泛使用的药物的功能影响以及这种影响可能如何增加的信息 青少年饮酒行为。

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.