ETHANOL DISCRIMINATION IN AGED FEMALE MONKEYS

老年雌性猴子的乙醇歧视

• 批准号: 8357827
• 负责人: Christa M Helms
• 金额: $ 3.63万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357827
• 关键词: Affect; Aging; Alcohol consumption; Cues; Data; Discrimination; Ethanol; Ethanol Metabolism; Female; Food; Funding; Grant; Health; Hormonal Change; Human; Mediating; Menopause; Monkeys; National Center for Research Resources; Neurotransmitters; Ovarian hormone; Ovary; Periodicity; Primates; Principal Investigator; Procedures; Progesterone; Research; Research Infrastructure; Resources; Risk; Role; Source; Stimulus; Taste Perception; Testing; Training; United States National Institutes of Health; Water; Women' s Role; age related; aged; aging population; alcohol effect; alcohol sensitivity; cost; drug discrimination; gamma-Aminobutyric Acid; male; nonhuman primate; receptor; reproductive hormone

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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 随着美国老龄化人口的增加，了解乙醇如何影响老年人尤为重要。与老年男性相比，老年女性因摄入乙醇对健康造成负面影响的风险更大。老年女性特有的荷尔蒙变化可能会导致乙醇效果的变化，其中包括对某些主观效果更加敏感。这项研究将加深我们对乙醇对老年女性神经药理学作用以及卵巢激素作用的了解。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）在年轻和老年雌性非人类灵长类动物之间存在差异，它们与人类具有相似的乙醇代谢和生殖激素周期性，2）因手术引起的更年期而改变。这些研究采用了一种操作程序，即药物辨别，训练受试者在鼻饲乙醇后按下一个杠杆，在水后按下另一个杠杆。如果没有味觉提示，受试者必须注意乙醇的主观或歧视性刺激效果。只有按下正确的控制杆后，食物才会被送达。训练后，测试受试者对乙醇和卵巢产生的三种黄体酮衍生物替代物的辨别刺激作用的敏感性，这些衍生物可正向调节 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及其神经药理学机制中的作用的信息。