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The role of D1/dDA1 and D5/DAMB dopamine receptors in ethanol induced behavioral disinhibition

机译:D1 / dDA1和D5 / DAMB多巴胺受体在乙醇诱导的行为抑制中的作用

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摘要

Alcohol drinking causes changes in behaviors by acting on various neurotransmitters (e.g. GABA, acetyl choline and glutamate) (Kumar et al., 2009), neuromodulators (e.g. dopamine, and serotonin) (Banerjee, 2014) and ion channels (e.g. Ca2+ and K channels) (Harris and Hood, 1980). Behaviors associated with alcohol consumption include loss of motor coordination, impaired decision-making, altered circadian rhythm, and disinhibited behaviors (NIH-NIAAA, Bethesda, MD). Behavioral disinhibition is defined as having poor judgment and acting in a manner that one would not usually behave (Greenspan and Ferveur, 2000) and commonly caused by substance abuse such as alcohol consumption and cocaine use. Excessive alcohol intake can also have detrimental impacts such as car accidents leading to death, violent attacks, and unsafe sexual behaviors. Furthermore, alcohol consumption affects the sleep cycle (Sharma et al., 2017), which could aggravate behavioral disinhibition. This research aims to identify the mechanism by which ethanol induces behavioral disinhibition. Drosophila melanogaster was used as a model organism for this study. Drosophila and mammals have similar behavioral responses to ethanol (Kong et al., 2010). Wild-type flies exhibit disinhibited inter-male courtship under the influence of ethanol and the level of disinhibited courtship increases with recurring ethanol exposure (Lee et al., 2008), which represents behavioral sensitization (Berger et al., 2004). Behavioral sensitization is an enhanced response to stimulus after multiple exposures and underlies drug addiction (Walker, 1999). Dopamine is a major neuromodulator in both flies and mammals and plays roles in reward, attention, learning, memory, motivation, sleep, and ethanol-induced disinhibition Oishi and Lazarus, 2017; van Gaalen et al., 2006). Additionally, dopamine is involved in the development of drug dependence and addiction (Volkow et al., 2009). To understand the mechanism by which dopamine mediates ethanol-induced behavioral disinhibition and sensitization, this study focused on the D1-family receptors dDA1 and DAMB, the insect homologs of mammalian D1 and D5 dopamine receptors, respectively. The major finding of this study is the essential role of DAMB receptor in alcohol-induced behavioral disinhibition. This may provide insight into new intervention strategies for alcohol abuse and addiction.
机译:饮酒会通过作用于各种神经递质(例如GABA,乙酰胆碱和谷氨酸)(Kumar等,2009),神经调节剂(例如多巴胺和5-羟色胺)(Banerjee,2014)和离子通道(例如Ca2 +和K)来改变行为。频道)(Harris和Hood,1980年)。与饮酒有关的行为包括运动协调能力丧失,决策受损,昼夜节律改变和行为失禁(NIH-NIAAA,贝塞斯达,马里兰州)。行为抑制被定义为判断力较差,并且以通常不会表现出来的方式行事(Greenspan和Ferveur,2000),并且通常是由滥用毒品(例如饮酒和使用可卡因)引起的。过量饮酒也会产生不利影响,例如导致死亡,暴力袭击和不安全性行为的车祸。此外,饮酒会影响睡眠周期(Sharma等,2017),这可能加剧行为抑制。这项研究旨在确定乙醇诱导行为抑制的机制。果蝇用作本研究的模型生物。果蝇和哺乳动物对乙醇的行为反应相似(Kong等,2010)。野生型果蝇在乙醇的影响下表现出抑制雄性间的求爱,随着反复暴露于乙醇,抑制型求爱的水平增加(Lee等,2008),这代表了行为敏感性(Berger等,2004)。行为敏化是多次接触后对刺激的增强反应,是药物成瘾的基础(Walker,1999)。多巴胺是果蝇和哺乳动物中的主要神经调节剂,在奖励,注意力,学习,记忆,动机,睡眠和乙醇引起的去抑制作用中发挥作用Oishi和Lazarus,2017年; van Gaalen等,2006)。此外,多巴胺也参与药物依赖性和成瘾的发展(Volkow等,2009)。为了了解多巴胺介导乙醇诱导的行为抑制和致敏作用的机制,本研究集中于D1家族受体dDA1和DAMB,分别是哺乳动物D1和D5多巴胺受体的昆虫同源物。这项研究的主要发现是DAMB受体在酒精诱导的行为抑制中的重要作用。这可以提供对酒精滥用和成瘾的新干预策略的见识。

著录项

  • 作者

    Mercado, Ivan.;

  • 作者单位

    The University of Texas at El Paso.;

  • 授予单位 The University of Texas at El Paso.;
  • 学科 Neurosciences.;Psychobiology.
  • 学位 M.S.
  • 年度 2017
  • 页码 66 p.
  • 总页数 66
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 语言学;
  • 关键词

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