Modulation of Alcohol Effects on Nervous System Function by Social Experience

社会经验调节酒精对神经系统功能的影响

• 批准号: 9387242
• 负责人: Jens Herberholz
• 金额: $ 7.6万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9387242
• 关键词: Acute; Affect; Aggressive behavior; Agonist; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcoholic Intoxication; Alcoholism; Alcohols; Aminobutyric Acids; Animal Behavior; Animal Model; Animals; Area; Astacoidea; Behavior; Behavior Therapy; Behavioral; Biological; Biological Models; Brain; Cause of Death; Cells; Characteristics; Complex; Confocal Microscopy; Development; Disease; Electrophysiology (science); Ethanol; Future; Goals; Health; Human; Individual; Injection of therapeutic agent; Interneurons; Intoxication; Invertebrates; Investigation; Knowledge; Lateral; Lead; Life Style; Link; Measures; Mediating; Modeling; Modification; Molecular; Nervous System Physiology; Nervous system structure; Neuraxis; Neurons; Neuropharmacology; Neurophysiology - biologic function; Neurotransmitters; Organism; Pharmaceutical Preparations; Pharmacological Treatment; Physiological; Preparation; Prevention; Preventive measure; Public Health; Recording of previous events; Regulation; Research; Research Activity; Risk; Sensory Receptors; Serotonin; Social Behavior; Social Dominance; Social Functioning; Social Interaction; Social isolation; Social status; Societies; Structure; System; Tail; Testing; Triad Acrylic Resin; Work; alcohol availability; alcohol effect; alcohol exposure; alcohol response; behavioral response; design; drug of abuse; effective therapy; experience; experimental study; gamma-Aminobutyric Acid; improved; individualized medicine; innovation; member; neural circuit; neurobehavioral; neurochemistry; neuromechanism; neurophysiology; receptor; relating to nervous system; response; serotonin receptor; social; statistics

Alcohol is the most abused drug in our society with devastating impact on both health and the economy. The aim of the proposed research activity is twofold: To gain a better understanding of the cellular mechanisms underlying the interaction between alcohol and nervous system function, and to elucidate how social experience modifies this interaction. The neurocellular effects of alcohol intoxication are still poorly understood. Unlike other drugs of abuse, alcohol does not act on one specific receptor in the central nervous system but changes neural activity by altering multiple neurotransmitter systems, e.g. by modifying the efficacy of brain receptors, including those for γ-aminobutyric acid (GABA) and serotonin (5-HT). The same neurochemicals have been implicated in the regulation of social behavior in humans and many non-human animals, especially in the context of aggression and social dominance. Social interactions with conspecifics cause differences in behavior and the corresponding neural circuits. However, how these socially mediated changes affect the interaction between alcohol and neural activity is unknown. A better understanding of the interplay between alcohol and neural circuitry that is shaped by social experience is crucial to improve prevention and individualized treatment options for alcohol-related health risks. This study proposes a combination of behavioral, neurophysiological, neurochemical, and neuroanatomical experiments to explore the effects of acute ethanol exposure in animals of different social status. Experiments will be performed in crayfish, an invertebrate model that features an accessible nervous system as well as identified neural circuitry that is known to be shaped by social experience and can be studied with a high level of experimental rigor. Our preliminary results show that crayfish are sensitive to alcohol exposure and display discrete behavioral changes with increasing intoxication (hyperexcitability is followed by inhibition). Surprisingly, we found that the behavioral changes are expressed more quickly in socially experienced animals compared to those previously isolated from conspecifics. In addition, these socially-shaped differences are paralleled in single-cell recordings of individual neurons. We hypothesize that different social experiences cause modifications of neural receptors that are targeted by alcohol, which produces the observed neurobehavioral changes in response to alcohol exposure. The proposed experiments will use animals of discrete social status (i.e., dominants, subordinates, isolates) to investigate the interplay between different neurotransmitter systems, alcohol, and social status. The results of these basic studies are expected to stimulate work in more complex model systems, which could lead to improvements of preventive measures for alcohol-related health risks as well as behavioral and pharmacological treatments for human alcoholism.

酒精是我们社会中最常滥用的药物，对健康和经济都有毁灭性的影响。这 拟议研究活动的目的有两个： 更好地了解细胞机制 酒精与神经系统功能之间相互作用的基础，并阐明社交如何 经验改变了这种互动。酒精中毒对神经细胞的影响仍然知之甚少。 与其他滥用药物不同，酒精不会作用于中枢神经系统中的一种特定受体，而是作用于中枢神经系统中的一种特定受体。 通过改变多个神经递质系统来改变神经活动，例如通过改变大脑的功效 受体，包括 γ-氨基丁酸 (GABA) 和血清素 (5-HT) 受体。相同的神经化学物质 与人类和许多非人类动物的社会行为调节有关，特别是 在侵略和社会统治的背景下。与同种人的社交互动会导致差异 行为和相应的神经回路。然而，这些社交媒介的变化如何影响 酒精和神经活动之间的相互作用尚不清楚。更好地理解之间的相互作用 酒精和由社会经验塑造的神经回路对于改善预防和预防至关重要。 针对与酒精相关的健康风险的个体化治疗方案。这项研究提出了一个组合 行为、神经生理学、神经化学和神经解剖学实验来探索 不同社会地位的动物急性乙醇暴露。实验将在小龙虾中进行 无脊椎动物模型，具有可访问的神经系统以及已识别的神经回路 众所周知，它是由社会经验塑造的，并且可以通过高水平的实验严谨性进行研究。我们的 初步结果表明，小龙虾对酒精暴露很敏感，并且表现出离散的行为 随着中毒程度的增加而变化（过度兴奋之后是抑制）。令人惊讶的是，我们发现 与以前相比，有社交经验的动物的行为变化表现得更快 与同种动物隔离。此外，这些社会形态的差异在单细胞记录中是平行的 单个神经元。我们假设不同的社会经历会导致神经受体的改变 以酒精为目标，产生对酒精反应的观察到的神经行为变化 接触。拟议的实验将使用具有离散社会地位的动物（即统治者、从属者、 分离株）来研究不同神经递质系统、酒精和社会地位之间的相互作用。这 这些基础研究的结果预计将刺激更复杂模型系统的工作，这可能 改进与酒精相关的健康风险以及行为和行为的预防措施 人类酒精中毒的药物治疗。