ETHANOL DISCRIMINATION IN AGED FEMALE MONKEYS

该子项目是利用资源的许多研究子项目之一 由NIH/NCRR资助的中心拨款提供。次级项目的主要支助 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 表示子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 随着美国老龄化人口的增加，了解乙醇对老年人的影响尤为重要。与老年男性相比，老年女性摄入乙醇对健康产生负面影响的风险更大。衰老女性特有的激素变化可能导致乙醇影响的变化，其中包括对某些主观影响的更大敏感性。这项研究将增加我们对乙醇在老年女性中的神经药理学作用和卵巢激素作用的理解。神经递质γ-氨基丁酸（GABA）对GABA（A）受体作用的正调节是乙醇药理作用的关键组成部分。我们的研究将确定介导乙醇效应的神经药理学机制是否1）在年轻和年老的雌性非人灵长类动物之间存在差异，这些灵长类动物具有与人类相似的乙醇代谢和生殖激素周期，以及2）通过药物诱导的绝经而改变。这些研究使用了一种操作性的程序，即药物辨别，在这种程序中，受试者被训练在鼻饲乙醇后按下一个杠杆，在水后按下另一个杠杆。在没有味觉线索的情况下，受试者必须注意酒精的主观或辨别性刺激效应。只有在按下正确的杠杆后，才能提供食物。在训练之后，测试受试者对乙醇的区别性刺激效应和由卵巢产生的正调节GABA（A）受体的三种孕酮衍生物的替代的敏感性。这些数据将提供关于卵巢激素在年龄相关的乙醇敏感性变化中的作用及其神经药理学机制的信息。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. As the U.S. aging population increases, it is especially important to understand how ethanol affects older people. Aged females are at greater risk for the negative health consequences of ethanol consumption compared to aged males. Hormonal changes specific to aging females could contribute to changes in the effects of ethanol, which include greater sensitivity to certain subjective effects. This research will increase our understanding of the neuropharmacologic effects of ethanol in aged females and the role ovarian hormones. Positive modulation of the effects of the neurotransmitter gamma-aminobutyric acid (GABA) at GABA(A) receptors is a critical component of the pharmacologic effects of ethanol. Our studies will determine whether the neuropharmacologic mechanisms mediating ethanol effects 1) differ between young and aged female non-human primates, which have similar ethanol metabolism and reproductive hormone cyclicity as humans, and 2) are altered by surgically-induced menopause. The studies are using an operant procedure, drug discrimination, in which subjects are trained to press one lever after nasogastric administration of ethanol and another after water. Without taste cues, subjects must attend to the subjective or discriminative stimulus effects of ethanol. A food treat is delivered only after presses to the correct lever. After training, the subjects are tested for sensitivity to the discriminative stimulus effects of ethanol and the substitution of three progesterone derivatives produced by the ovaries that positively modulate GABA(A) receptors. These data will provide information about the role of ovarian hormones in age-related changes in sensitivity to ethanol and its neuropharmacologic mechanisms.