Age differences in ethanol discrimination: Role of GABA-A and NMDA receptors

乙醇歧视中的年龄差异：GABA-A 和 NMDA 受体的作用

基本信息

批准号：
8255802
负责人：
Rachel Ivy Anderson
金额：
$ 3.03万
依托单位：
STATE UNIVERSITY OF NY,BINGHAMTON
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8255802
关键词：
Accounting Adolescence Adolescent Adult Affinity Age Agonist Alcohol consumption Alcohols Aminobutyric Acids Animal Model Animal Testing Animals Attenuated Biological Assay Brain region Development Diazepam Discrimination Discrimination Learning Dose Ethanol GABA-A Receptor Growth Impairment Injection of therapeutic agent Intake Life Messenger RNA Modeling Motivation N-Methyl-D-Aspartate Receptors N-Methylaspartate Procedures Property Proteins Rattus Relative (related person)Reporting Rodent Rodent Model Role Sedation procedure Staging Stimulus Synapses Synaptic Receptors System Testing Time TimeLine Training Work age difference age related alcohol cue alcohol sensitivity classical conditioning drug discrimination dysphoria ethanol-induced social facilitation gamma-Aminobutyric Acid ifenprodil insight male mature animal motor impairment neglect psychopharmacologic receptor relating to nervous system social

项目摘要

Adolescence is a developmental period during which high ethanol use is common. Studies using rodent models of adolescence have observed age-related differences in sensitivity to many of ethanol's properties, including greater sensitivity of adolescents than adults to ethanol-induced social facilitation, but attenuated sensitivity to ethanol- induced motor impairment, sedation, and dysphoria. Such age discrepancies in sensitivity suggest that adolescents and adults may perceive ethanol's subjective effects differently. Ethanol discrimination procedures have been used extensively to gain insight into the interoceptive (i.e., subjective) properties of ethanol, but studies using such procedures have largely neglected adolescent subjects. Using an established animal model of adolescence, the proposed work aims to characterize the ethanol cue in adolescent rats relative to adults using a Pavlovian conditioned approach drug discrimination procedure amenable to testing animals within the relatively short developmental period of adolescence. This procedure will allow for comparison of discrimination acquisition in adolescents and adults under a variety of training conditions that will take into account age differences in ethanol sensitivity. Given that GABAA and NMDA receptor systems have been identified as major contributors to the ethanol cue in adult animals, psychopharmacological studies will then examine the role of developmental alterations in GABAA and NMDA subunit composition in the ethanol cue in animals of each age by testing subunit-specific compounds in ethanol substitution tests and quantifying subunit expression in specific brain regions across age using both mRNA and protein assays.

青春期是一个发育时期，大量使用乙醇是很常见的。使用青春期啮齿动物模型的研究观察到，对许多乙醇特性的敏感性存在与年龄相关的差异，包括青少年比成年人对乙醇引起的社交促进作用更敏感，但对乙醇引起的运动障碍、镇静和烦躁不安的敏感性减弱。这种敏感性的年龄差异表明青少年和成年人可能对乙醇的主观影响有不同的看法。乙醇歧视程序已被广泛用于深入了解乙醇的内感受（即主观）特性，但使用此类程序的研究在很大程度上忽略了青少年受试者。使用已建立的青春期动物模型，拟议的工作旨在使用巴甫洛夫条件方法药物辨别程序来表征青春期大鼠相对于成年人的乙醇线索，该程序适合在相对较短的青春期发育期内测试动物。该程序将允许在考虑乙醇敏感性的年龄差异的各种训练条件下比较青少年和成人的歧视获得。鉴于 GABAA 和 NMDA 受体系统已被确定为成年动物乙醇提示的主要贡献者，精神药理学研究将通过测试亚基来检查每个年龄动物乙醇提示中 GABAA 和 NMDA 亚基组成的发育变化的作用。乙醇替代测试中的特定化合物，并使用 mRNA 和蛋白质测定定量特定大脑区域中不同年龄的亚基表达。