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尚未得到广泛研究。本实验室的研究表明，在青春期接触酒精的成年大鼠的皮质、海马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，这可能是在青少年酗酒者身上观察到的。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，因为它们对乙醇的敏感性增加。NMDA受体在大脑区域的注意力和记忆功能的调节中也起着重要作用，这些区域已被证明会因青少年酒精暴露而受损。这一提议的主要假设是：乙醇通过诱导NMDA系统的持续上调，对青少年施加其独特的影响。因此，乙醇戒断和神经退行性变的发展在青少年中得到加强。此外，这种NMDA上调持续到成年期，并有助于青少年酒精暴露后观察到的长期神经生理和认知缺陷。本应用程序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乙醇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来实现的：

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