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

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 和蛋白质测定定量不同年龄特定大脑区域的亚基表达，来研究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。

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.