Modulation of Alcohol Effects on Nervous System Function by Social Experience

酒精是我们社会中滥用最多的药物，对健康和经济都有毁灭性的影响。的 拟议的研究活动的目的是双重的：为了更好地了解细胞机制， 酒精和神经系统功能之间相互作用的基础，并阐明社会 经验改变了这种相互作用。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5-羟色胺（5-HT）受体。同样的神经化学物质 与人类和许多非人类动物的社会行为的调节有关，特别是 在侵略和社会支配的背景下。与同种动物的社会互动会导致 行为和相应的神经回路。然而，这些社会介导的变化如何影响 酒精和神经活动之间的相互作用是未知的。更好地理解 酒精和由社会经验塑造的神经回路对于改善预防至关重要， 针对酒精相关健康风险的个性化治疗方案。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，以探索 不同社会地位动物的急性乙醇暴露。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识别的神经回路， 众所周知，这是由社会经验塑造的，可以用高水平的实验严谨性来研究。我们 初步结果表明，小龙虾对酒精敏感， 随着中毒程度的增加而变化（兴奋过度后是抑制）。令人惊讶的是，我们发现， 行为变化在有社会经验的动物中表现得更快， 与同类分离。此外，这些社会形态的差异在单细胞记录中也被掩盖了。 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 这些神经元被酒精所针对，从而产生对酒精的反应， exposure.拟议的实验将使用离散社会地位的动物（即，支配者，从属者， 分离），以调查不同的神经递质系统，酒精和社会地位之间的相互作用。的 这些基础研究的结果有望刺激更复杂模型系统的工作， 导致改善预防措施，以防止与酒精有关的健康风险以及行为和 人类酒精中毒的药物治疗

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.