Role of BLA kappa opioid receptors in adolescent anxiety and ethanol consumption

BLA kappa 阿片受体在青少年焦虑和乙醇消耗中的作用

基本信息

批准号：
9357489
负责人：
Marvin Rafael Diaz
金额：
$ 7.81万
依托单位：
STATE UNIVERSITY OF NY,BINGHAMTON
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-25 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9357489
关键词：
Acute Adolescence Adolescent Adult Age Agonist Alcohol abuse Alcohol consumption Alcohols Amygdaloid structure Anti-Anxiety Agents Anxiety Applications Grants Behavior Behavioral Brain Cells Chemosensitization Darkness Data Development Dynorphins Electrophysiology (science)Equilibrium Ethanol Exposure to Foundations Future Glutamates Goals In Vitro Interneurons Light Long-Term Potentiation Mediating Mediator of activation protein Microinjections Mus Neurons Opioid Output Play Process Property Receptor Activation Receptor Signaling Regulation Reporting Rewards Rodent Role Slice Structure System Teratogens Testing Time adolescent alcohol exposure age related alcohol effect alcohol exposure alcohol seeking behavior anxiety-like behavior drinking experimental study gamma-Aminobutyric Acid hippocampal pyramidal neuron innovation kappa opioid receptors mature animal neural circuit neurobehavioral neurobiological mechanism neuromechanism neurophysiology novel patch clamp receptor receptor function relating to nervous system response transmission process

项目摘要

Ethanol use is a common occurrence worldwide, and the onset of ethanol exposure is a major contributing factor to ethanol abuse. Adolescence is a developmental period when ethanol use is typically initiated, making it a highly vulnerable time to predispose future abuse and alterations in neurobehavioral function. Moreover, adolescents consume more ethanol per drinking session than adults, perhaps due to the greater sensitivity to the anxiolytic properties of ethanol during this highly stressful and anxiety-provoking developmental stage. However, the neurobiological mechanisms of acute ethanol in adolescents are poorly understood. The opioid system is a major target of ethanol and kappa opioid receptors (KORs), particularly, have been shown to play a major role in the neurophysiological effects of ethanol in the reward and anxiety circuits. The basolateral amygdala (BLA), a key structure of the reward and anxiety circuits, is involved in ethanol-seeking behaviors. Specifically, alterations in GABA transmission within the BLA are associated with the anxiolytic properties of ethanol and ethanol-seeking. Importantly, KOR activation modulates BLA excitability and anxiety-like behaviors in an age-dependent manner, suggesting that KORs may significantly contribute to the increased sensitivity to the anxiolytic properties of ethanol in adolescents, which may drive increased ethanol consumption in adolescence. Thus, the overarching goal of this proposal is to test the interactions between BLA KORs and ethanol consumption in adolescents. Importantly, preliminary findings indicate that a KOR agonist potentiates GABAergic transmission within the BLA of adolescents, but not adults, and this effect is similar to that of acute ethanol. This suggests that ethanol may hijack the KOR system, thereby resulting in anxiolysis, which helps promote ethanol consumption in adolescents. Two Specific Aims will (1) determine the functional interactions between BLA KOR activation and acute ethanol in vitro and (2) examine the interaction of BLA KORs and acute ethanol on anxiety-like behavior and ethanol consumption. These innovative studies will test novel and unique hypotheses surrounding the developmental differences of ethanol and describe neural mechanisms specific to adolescent ethanol exposure.

乙醇的使用是全球常见的，乙醇的发作是主要的促成乙醇滥用的因素。青春期是使用乙醇的发展时期通常是启动的，使其成为易受未来虐待和神经行为功能的改变。此外，青少年消耗更多的乙醇饮酒时间比成人，也许是由于对在这个高度压力和焦虑的发育阶段，乙醇。但是，青少年急性乙醇的神经生物学机制知之甚少。阿片类药物系统是乙醇和Kappa阿片受体（KOR）的主要目标，尤其是证明在乙醇中在奖励和焦虑中的神经生理作用中起主要作用电路。基底外侧杏仁核（BLA）是奖励和焦虑电路的关键结构，是参与寻求乙醇的行为。具体而言，GABA传输的变化 BLA与乙醇和寻求乙醇的抗焦虑特性有关。重要的是， KOR激活调节BLA兴奋性和焦虑症的行为方式表明，科尔斯可能会显着有助于提高对青少年乙醇的抗焦虑特性，这可能会促进乙醇消耗量增加在青春期。因此，该提案的总体目标是测试青少年的bla kors和乙醇消耗。重要的是，初步发现表明 Kor激动剂会增强青少年BLA内的Gabaergic传播成人，这种作用与急性乙醇相似。这表明乙醇可能会劫持 kor系统，从而导致焦虑分析，这有助于促进乙醇消耗青少年。两个具体目标将（1）确定Bla Kor之间的功能相互作用体外激活和急性乙醇，（2）检查BLA KOR和急性的相互作用乙醇类似焦虑症的行为和乙醇消耗。这些创新的研究将测试围绕乙醇和描述针对青少年乙醇暴露的神经机制。