Biological Basis of Conditioned Cues Effects on EtOH-Seeking

条件线索对乙醇寻求影响的生物学基础

基本信息

批准号：
8487325
负责人：
ZACHARY Aaron RODD
金额：
$ 29.02万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8487325
关键词：
Alcohol consumption Alcoholism Alcohols Amygdaloid structure Animal Model Behavior Biological Brain region Characteristics Chronic Chronic Disease Complex Cues Development Disease Dopamine Dopamine D1 Receptor Environment Exposure to FOS gene Glutamates Goals Intercalated Cell Interneurons Investigation Mediating Microinjections Modeling N-Methylaspartate Neurobiology Neurons Neuropharmacology Neurotransmitters Pathway interactions Performance Pharmaceutical Preparations Rattus Recovery Relapse Serotonin Stimulus System Testing Ventral Tegmental Area alcohol craving alcohol relapse alcoholism therapy base craving dopaminergic neuron drinking drinking behavior extracellular gamma-Aminobutyric Acid innovation neural circuit neurochemistry non-drug prevent problem drinker receptor research study response therapeutic development treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Alcoholism is a chronic disorder characterized by repeated episodes of relapse to alcohol consumption. Potential precipitators of relapse include cues paired with past alcohol use. Subsequent exposure to these stimuli could induce a state of alcohol craving that results in reinstatement of alcohol us. The goals of this proposal are to determine the biological bases of how conditioned cues elicit or inhibit drug-seeking. The long- range objectives of this study are to determine the neurocircuits that regulate the modulation of EtOH-seeking by conditioned cues. The overall hypotheses are that there are two distinct systems that integrate environmental cues that promote or inhibit EtOH-seeking, and that each system is comprised of separate neurocircuits and neurotransmitter systems. These hypotheses will be tested primarily using the alcohol- preferring (P) rat, which demonstrates high alcohol drinking behavior and robust EtOH-seeking and relapse behaviors. Proposed experiments will determine the effects of environmental cues (conditioned excitation and conditioned inhibition) on the expression of context-induced seeking. Proposed experiments will determine the neurochemical consequences of exposure to conditioned cues that promote or inhibit EtOH-seeking. In addition, the proposed experiments will identify the neurotransmitter characteristics of neurons activated by presentation of cues that promote or inhibit EtOH-seeking. Further experiments will determine the effects of altering activity at candidate receptors in discrete brai regions on the ability of conditioned cues to alter EtOH- seeking. Understanding the complex factors that underlie EtOH-seeking behaviors and the ability of environmental cues to potentiate or suppress EtOH-seeking will contribute toward the development of therapeutic strategies to reduce 'craving' and alcohol relapse.

描述（由申请人提供）：酒精中毒是一种慢性疾病，其特征是反复复发到酒精消耗。复发的潜在降水剂包括与过去的酒精使用配对的提示。随后暴露于这些刺激可能会引起渴望的饮酒状态，从而导致我们恢复我们的酒精。该提案的目标是确定条件提示如何引起或抑制寻求药物的生物学基础。这项研究的长距离目标是确定根据条件提示调节寻求EtoH寻求ETOH的神经电路。总体假设是，有两个不同的系统整合了促进或抑制寻求EtOH的环境线索，并且每个系统都由单独的神经电路和神经递质系统组成。这些假设将主要使用酒精优先（P）大鼠进行检验，该假设表明饮酒行为高，寻求良好的EtOH和复发行为。提出的实验将确定环境线索（条件激发和条件抑制）对上下文引起的寻求表达的影响。提出的实验将确定暴露于促进或抑制寻求EtOH的条件提示的神经化学后果。此外，提出的实验将通过呈现促进或抑制寻求EtOH的提示激活的神经元的神经递质特征。进一步的实验将确定离散Brai区域中候选受体的活性改变的影响，对有条件提示改变EtoH的能力。了解基于寻求ETOH的行为的复杂因素以及环境线索增强或抑制寻求EtoH的能力将有助于制定治疗策略，以减少“渴望”和酒精复发。