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

青春期是一个发育期，在此期间，高乙醇使用是常见的。使用青春期啮齿动物模型的研究已经观察到对许多乙醇性质的敏感性的年龄相关差异，包括青少年比成年人对乙醇诱导的社会促进的敏感性更高，但对乙醇诱导的运动损伤、镇静和烦躁的敏感性减弱。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。乙醇辨别程序已被广泛用于深入了解内感受性（即，主观的）乙醇的性质，但使用这种程序的研究在很大程度上忽略了青少年的主题。使用一个已建立的动物模型的青春期，拟议的工作的目的是表征乙醇线索在青春期大鼠相对于成年人使用巴甫洛夫条件反射的方法药物歧视程序适合测试动物在相对较短的发育期的青春期。该程序将允许在各种训练条件下比较青少年和成年人的辨别力，这些训练条件将考虑乙醇敏感性的年龄差异。鉴于GABAA和NMDA受体系统已被确定为成年动物中乙醇线索的主要贡献者，精神药理学研究将通过在乙醇替代试验中测试亚基特异性化合物并使用mRNA和蛋白质测定定量各年龄段特定脑区中的亚基表达，来检查每个年龄段动物中乙醇线索中GABAA和NMDA亚基组成的发育改变的作用。

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.