ETHANOL DISCRIMINATION IN AGED FEMALE MONKEYS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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。这项拟议的研究将增加我们对乙醇对老年女性的神经药理学效应以及卵巢激素作用的理解。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。拟议中的研究将确定乙醇效应的神经药理学机制是否有差异：1)年轻和老年雌性非人类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。这些研究将使用一种可操作的程序，即药物辨别，在此过程中，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，受试者将被测试对乙醇的区别刺激效应的敏感度，以及卵巢产生的三种孕酮衍生物对GABA(A)受体的积极调节作用。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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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. The proposed 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. The proposed 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 will use 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 will be 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.