ETHANOL DISCRIMINATION IN AGED FEMALE MONKEYS

这个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。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级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，老年女性饮酒带来的负面健康后果的风险更大。老年女性特有的荷尔蒙变化可能会导致酒精影响的变化，包括对某些主观影响更敏感。这项研究将增加我们对乙醇在老年女性中的神经药理作用以及卵巢激素的作用的了解。神经递质γ-氨基丁酸(GABA)对GABA(A)受体的正向调节作用是乙醇药理作用的重要组成部分。我们的研究将确定乙醇效应的神经药理学机制是否不同：1)年轻和老年雌性非人灵长类动物的乙醇代谢和生殖激素循环性与人类相似，2)手术诱导的更年期改变。这项研究使用了一种可操作的程序--药物辨别，在这种程序中，受试者被训练在鼻胃注射乙醇后按下一个杠杆，在给水后按下另一个杠杆。在没有味觉提示的情况下，受试者必须注意酒精的主观或歧视性刺激效应。只有按到正确的操纵杆后，才能送出食物。训练结束后，受试者被测试对乙醇的区别刺激效应的敏感性，以及由卵巢产生的三种孕酮衍生物的替代，这些衍生物正向调节GABA(A)受体。这些数据将提供有关卵巢激素在与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.