ANATOMICAL LOCALIZATION OF ETHANOL'S DISCRIMINATIVE STIMULUS EFFECTS

乙醇区别性刺激效应的解剖学定位

基本信息

批准号：
6563223
负责人：
LINDA J. PORRINO
金额：
$ 17.85万
依托单位：
WAKE FOREST UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-01-01 至 2002-12-31
项目状态：
已结题

项目摘要

Ingested alcohol produces a constellation of discernible subjective effects that are believed to be the result of ethanol's actions on multiple receptor systems at a variety of neuroanatomical sites in the central nervous system. Although the behavioral paradigm of drug discrimination has been used extensively to characterize the neuropharmacological mechanisms that mediate the interoceptive cues produced by ethanol, the neuroanatomical substrates responsible for these cues have received little attention. The goal of these experiments is to identify the network of neural activity that is responsible for the perceptible interoceptive cues that are used by the animal to distinguish ethanol from water in the drug discrimination paradigm. We will first establish the pattern of functional activity in the CNS associated with the discrimination of a low dose (1 g/kg) of ethanol. The purpose of the second set of experiments is to characterize the patterns of activity produced by the administration of higher and lower doses of ethanol that produce varying degrees of ethanol-appropriate responding. Finally, we will determine the neuroanatomical substrates of the effects of drugs with actions at the GABAA receptor complex that reliably produce ethanol-like cues, as well as determine the substrates of the effects of antagonist drugs with actions at the NMDA receptor complex that reliably produce ethanol-like cues. These experiments will provide a more complete understanding of neurobiological basis of the stimulus effects of ethanol responsible for the perceptible interoceptive cues that are used by the animal to distinguish ethanol from water in the drug discrimination paradigm.

摄入的酒精会产生一系列可辨别的主观作用，这被认为是乙醇对中枢神经系统中各种神经解剖部位的多个受体系统作用的结果。尽管药物歧视的行为范式已被广泛用于表征介导乙醇产生的互感提示的神经药理机制，但负责这些线索的神经解剖基底物很少受到关注。这些实验的目的是确定导致动物用来区分乙醇与药物歧视范式中水的可感知性互感线索的神经活动网络。我们将首先建立与乙醇低剂量（1 g/kg）歧视有关的中枢神经系统中的功能活性模式。第二组实验的目的是表征通过给予较高和较低剂量的乙醇产生的活性模式，这些乙醇产生不同程度的乙醇响应。最后，我们将通过在GABAA受体复合物中可靠地产生类似乙醇的线索的作用来确定药物作用的神经解剖学底物，并确定拮抗剂药物对NMDA受体复合物的作用的作用的底物，从而可靠地产生乙醇样线索。这些实验将对乙醇的刺激效应的神经生物学基础有更全面的了解，这些乙醇对动物用来将乙醇与药物歧视范式中的水区分开的可感知性互感提示。