Neurobehavioral Consequences of Adolescent Alcohol

描述(由申请人提供)：青少年酗酒是一个严重的健康问题。然而，在动物模型中，青少年酒精暴露的长期后果还没有得到广泛的研究。该实验室的研究表明，青春期接触酒精的成年大鼠大脑皮质、海马体和基底前脑功能受损。这些神经生理缺陷指向注意力和记忆功能的缺陷，这可能是青少年酗酒者观察到的情况。青少年N-甲基-D-天冬氨酸(NMDA)受体系统可能在乙醇对青少年的独特影响中发挥关键作用，因为他们对乙醇的敏感性增加。NMDA受体还在调节大脑区域的注意力和记忆功能方面发挥着重要作用，这些区域已被证明受到青少年酒精暴露的损害。支持这一建议的主要假设是：乙醇通过诱导NMDA系统的持久上调而对青少年产生独特的影响。因此，青少年的酒精戒断和神经变性的发展是加速的。此外，这种NMDA上调持续到成年，并导致青少年酒精暴露后观察到的长期神经生理和认知缺陷。本申请中提出的研究使用行为、细胞/组织化学和神经生理学技术来检查酒精依赖的发展和青少年酒精暴露的持久神经行为后果。本应用程序的目标是通过以下具体目标实现的： 目的1.探讨青春期酒精依赖的发生发展。 目的2.研究青少年酒精暴露的行为后果，重点是持续注意力和工作记忆。 目的3：研究青少年酒精暴露持续神经行为后果的神经化学基础，重点研究NMDA系统

DESCRIPTION (provided by applicant): Adolescent alcohol abuse is a significant health concern. However, the long-term consequences of adolescent alcohol exposure in animal models have not been extensively examined. Studies from this laboratory demonstrate impaired cortical, hippocampal, and basal forebrain function in adult rats exposed to alcohol during adolescence. These neurophysiological deficits point towards deficits in attention and memory function, which may model those observed in adolescent alcohol abusers. Adolescent N-methyI-D-asparate (NMDA) receptor systems are likely to play a key role in ethanol's unique effects on the adolescent due to their increased sensitivity to ethanol. NMDA receptors also play an important role in the regulation of attention and memory function in brain regions, which have been demonstrated to be impaired by adolescent alcohol exposure. The principal hypothesis underlying this proposal is: Ethanol exerts its unique effects on the adolescent by inducing a lasting upregulation of NMDA systems. As a consequence, the development of ethanol withdrawal and neurodegeneration is enhanced in adolescents. Furthermore, this NMDA upregulation persists into adulthood and contributes to the long-term neurophysiological and cognitive deficits observed following adolescent alcohol exposure. The studies proposed in this application examine the development of ethanol dependence and the lasting neurobehavioral consequences of adolescent ethanol exposure using behavioral, cellular/histochemical, and neurophysiological techniques. The goals of this application are accomplished through the following specific aims: AIM 1. To investigate the development of ethanol dependence during adolescence. AIM 2. To investigate the behavioral consequences of adolescent ethanol exposure, with a focus on sustained attention and working memory. AIM 3: To investigate the neurochemical substrates underlying the lasting neurobehavioral consequences of adolescent ethanol exposure, with a focus on NMDA systems