Juvenile alcohol exposure: Neurobehavioral consequences

青少年酒精暴露：神经行为后果

• 批准号: 7016841
• 负责人: RATNA SIRCAR
• 金额: $ 5.85万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7016841
• 关键词: NMDA receptors; adolescence (12-20); age difference; alcoholism /alcohol abuse; behavior test; behavioral /social science research tag; biological signal transduction; central nervous system; cues; gender difference; glycine receptors; laboratory rat; learning; memory; neural plasticity; neuropsychology; psychopharmacology; substance abuse related behavior

DESCRIPTION (provided by applicant): Alcohol is the number one abused substance among adolescents. Several studies have shown that when adolescents use alcohol, they become excessive users of alcohol, and of other substances of abuse, later in life. Adolescents differ from adults in their response to alcohol in exhibiting less sensitivity to the sedative and motor impairing effects. Adolescent rats exhibit more tolerance to alcohol-induced hypothermia, and greater impairments in spatial memory than adult rats. In adolescent rats, the N-methyI-D-aspartate (NMDA) receptor-mediated synaptic plasticity in the hippocampus is more sensitive to alcohol than adults. Although differences in alcohol sensitivity between adolescent and adult rats have been established, the temporal effect of acute and repeated alcohol exposure during the adolescent period on spatial learning and memory remains unknown. The goal of the proposed study is to investigate the short- and long-term effects of alcohol exposure during the adolescent period on spatial memory. Hypotheses to be tested are: (1) alcohol exposure in adolescent rats cause impairments in spatial memory, (2) behavioral effects of repeated alcohol exposure in adolescent rats are long-term, (3) behavioral effects of alcohol exposure in adolescent rats differ from those in immature and adult rats, and (4) deficits in adolescent alcohol-induced spatial memory are associated with alterations in the NMDA receptor-channel complex. Rats will be exposed to acute and repeated alcohol treatments during the adolescent period and tested for deficits in the reference and visual spatial memory tasks in the Morris Water Maze. Others have already identified specific interactions between alcohol and the major neurotransmitter systems such as glutamate, GABA, dopamine, serotonin, endogenous opioids. In this proposal, adolescent alcohol exposure on the NMDA receptor-channel complex will be investigated. The proposed studies will identify neuroadaptive changes of early alcohol exposure and define the plasticity of the central nervous system during the adolescent period.

描述（由申请人提供）： 酒精是青少年中滥用的第一大物质。多项研究表明，当青少年饮酒时，他们会在以后的生活中过度饮酒和滥用其他物质。青少年对酒精的反应与成年人不同，他们对酒精的镇静和运动损害作用不太敏感。与成年大鼠相比，青春期大鼠对酒精引起的体温过低表现出更强的耐受性，并且空间记忆受损更大。在青春期大鼠中，海马 N-甲基-D-天冬氨酸 (NMDA) 受体介导的突触可塑性比成年大鼠对酒精更敏感。尽管青少年和成年大鼠之间的酒精敏感性存在差异，但青少年时期急性和反复接触酒精对空间学习和记忆的时间影响仍不清楚。拟议研究的目的是调查青少年时期酒精暴露对空间记忆的短期和长期影响。要测试的假设是：（1）青春期大鼠的酒精暴露会导致空间记忆受损，（2）青春期大鼠反复酒精暴露的行为影响是长期的，（3）青春期大鼠酒精暴露的行为影响不同于(4) 青少年酒精引起的空间记忆缺陷与 NMDA 受体通道复合体的改变有关。老鼠将在青少年时期接受急性和反复的酒精治疗，并在莫里斯水迷宫中测试参考和视觉空间记忆任务的缺陷。其他人已经确定了酒精和主要神经递质系统（如谷氨酸、GABA、多巴胺、血清素、内源性阿片类药物）之间的特定相互作用。在此提案中，将研究青少年酒精暴露对 NMDA 受体通道复合物的影响。拟议的研究将确定早期酒精暴露的神经适应性变化，并确定青少年时期中枢神经系统的可塑性。