Behavioral and molecular characterization of oxytocin's effect on alcohol consumption

催产素对饮酒影响的行为和分子特征

基本信息

  • 批准号:
    10380613
  • 负责人:
  • 金额:
    $ 2.38万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-04-01 至 2022-06-17
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY: Despite the prevalence and devastating impact of alcohol use disorder (AUD), only three FDA approved pharmacotherapies exist and even fewer have proved efficacious. Thus, development of new pharmacotherapies is necessary. Of crucial importance in designing such therapies are the complex interactions of alcohol-related behaviors with the social environment, demonstrating the need for incorporating social paradigms in alcohol consumption studies. Our laboratory utilizes the unique Herdsman cage system to allow for precise, individualized measurements of both consumption and behavior in a truly social setting. Oxytocin (oxt), a hormone with crucial roles in a variety of social behaviors has drawn attention as a promising pharmacotherapy for AUD with its implicated role in mediating the processes associated with drug use, as well as its social effects, which may serve to bolster abstinence. Oxt has been shown to be effective in decreasing alcohol consumption in rodents and alcohol craving in humans. Our laboratory recently demonstrated robust effects of repeated oxt treatment in decreasing alcohol consumption in the prairie vole (Microtus ochrogaster) - a socially monogamous rodent species with demonstrated translational validity to humans through common mechanisms regulating social behaviors. Given the pharmacotherapeutic potential of oxt, it is essential to characterize the behavioral and molecular mechanisms of oxt's demonstrated ability to decrease alcohol consumption. We aim to characterize the behavioral mechanisms of oxt's effect using our Herdsman system to examine whether oxt's effects on alcohol consumption are direct or mediated by increased social interaction. We also seek to demonstrate, for the first time in prairie voles, expression patterns of the receptor for advanced glycation end products (RAGE) in the brain and transport of oxt across the blood brain barrier (BBB) facilitated by RAGE using a selective antagonist. Finally, we aim to identify through which receptor oxt is exerting its effect using selective Oxtr knock out (KO) prairie voles generated using CRISPR/Cas9. We aim to examine possible sex differences throughout our investigation. These experiments will explicate oxt's role in mediating the reward processes associated with drug use and social behavior, particularly within the context of alcohol, and serve to clarify whether oxt is a promising target for pharmacotherapy for AUD.
项目摘要:尽管酒精使用障碍(AUD)的流行和破坏性影响,但只有 FDA批准的药物疗法有三种,被证明有效的就更少了。因此,发展 新的药物疗法是必要的。在设计这样的疗法中至关重要的是复杂的 酒精相关行为与社会环境的相互作用,证明了纳入的必要性 饮酒研究中的社会范式。我们的实验室利用独特的牧民笼子系统 允许在真正的社交环境中对消费和行为进行精确的、个性化的测量。 催产素(Oxt)是一种在多种社会行为中起关键作用的激素,作为一种很有前途的激素已引起人们的关注。 AUD的药物治疗及其在调节与药物使用相关的过程中的牵连作用 因为它的社会影响,这可能有助于支持节欲。OXT已被证明在减少 啮齿动物的酒精摄入量和人类的酒精渴求。我们的实验室最近表现出了强大的生命力 反复OXT处理对降低草原田鼠饮酒量的影响-- 一种社会上一夫一妻制的啮齿动物物种,通过共同的 规范社会行为的机制。鉴于OXT的药物治疗潜力,有必要 OXT表现出的减少酒精的行为和分子机制的特征 消费。我们的目标是利用我们的牧民系统来表征OXT影响的行为机制 研究一下奥施康定对酒精消费的影响是直接的,还是通过增加社会互动来实现的。 我们还首次试图在草原田鼠身上展示其受体的表达模式。 脑内晚期糖基化终产物(RAGE)与牛血脑屏障(BBB)的转运 在愤怒的帮助下使用选择性的拮抗剂。最后,我们的目标是确定通过哪个受体oxt 利用CRISPR/CAS9产生的选择性OXTR基因敲除(KO)草原田鼠发挥其作用。我们的目标是 在整个调查过程中检查可能的性别差异。这些实验将阐明OXT在 调解与吸毒和社会行为有关的奖励过程,特别是在 酒精,并用于澄清OXT是否是AUD药物治疗的有前景的靶点。

项目成果

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Sheena Potretzke其他文献

Sheena Potretzke的其他文献

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{{ truncateString('Sheena Potretzke', 18)}}的其他基金

Behavioral and molecular characterization of oxytocin's effect on alcohol consumption
催产素对饮酒影响的行为和分子特征
  • 批准号:
    10231974
  • 财政年份:
    2021
  • 资助金额:
    $ 2.38万
  • 项目类别:

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