Synaptic and Behavioral Correlates of Adeonsinergic Signaling in the BLA

BLA 中腺苷酸信号传导的突触和行为相关性

• 批准号: 8702978
• 负责人: Andrew Ryan Rau
• 金额: $ 3.67万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-22 至 2015-05-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8702978
• 关键词: Acute; Adenosine; Adolescent; Agonist; Alcohol consumption; Alcoholism; Amygdaloid structure; Animal Model; Animals; Anti-Anxiety Agents; Anxiety; Anxiety Disorders; Attenuated; Behavior; Behavioral; Behavioral Assay; Brain region; Characteristics; Chronic; Clinical; Comorbidity; Complex; Data; Development; Disease; Doctor of Philosophy; Ethanol; Fellowship; Funding; Glutamates; Goals; Health Sciences; Housing; Human; Individual; Investigation; Knowledge; Laboratories; Lead; Life Stress; Link; Literature; Mediating; Modeling; Monkeys; National Research Service Awards; Neuraxis; Neurobiology; Neuromodulator; Outcome; Pathway interactions; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacology; Pharmacotherapy; Physiological; Physiology; Play; Property; Publishing; Purinergic P1 Receptors; Rattus; Regulation; Research; Research Training; Rodent; Rodent Model; Role; Self Administration; Series; Signal Transduction; Site; Social isolation; Specificity; Synapses; Synaptic Transmission; System; Testing; Therapeutic; Time; Treatment Protocols; Universities; Withdrawal; Work; addiction; adenosine receptor activation; alcohol effect; alcohol exposure; alcohol use disorder; analog; base; catalyst; design; effective therapy; follow-up; forest; insight; interest; neurotransmission; novel; postsynaptic; pre-doctoral; preclinical study; presynaptic; receptor; relating to nervous system; research study; transmission process

DESCRIPTION (provided by applicant): This application for a Ruth L. Kirschstein NRSA for Individual Predoctoral Fellowship is submitted by Andrew R. Rau in order to seek funding for research training under the guidance of Jeff L. Weiner, Ph.D. in the Department of Physiology and Pharmacology at Wake Forest University Health Sciences. Research in the laboratory of Dr. Weiner is focused on unraveling the mechanisms responsible for the complex synaptic and behavioral effects of ethanol and anxiety related disorders. The research studies proposed in this application are intended to, for the first time characterize the role of adenosine (ADO) in regulating synaptic transmission within the basolateral amygdala (BLA). Moreover, these studies will further our understanding of adenosine's role in the neurobiological underpinnings associated with a model of early life stress that is associated with marked increases in anxiety-like behavior and ethanol consumption. Adenosine generally exerts its inhibitory effects by activating presynaptic A1 receptors which inhibit glutamate release. To that end, it would be of critical therapeutic benefit if this was the case in the BLA, as excessive excitability in this region has been directly linked to the manifestation of anxiety-like behaviorsin rodents, monkeys, and humans. Therefore this proposal outlines a series of experiments designed to characterize ADO's actions in the BLA and to investigate the behavioral outcomes of intra-BLA delivery of ADO agonists and antagonists. Briefly, Aim 1 will follow up on preliminary findings to identify the ADO receptor subtypes that mediate ADO modulation of BLA synaptic transmission. This aim will also test the hypothesis that tonic adenosinergic tone actively regulates excitatory transmission in the BLA. This aim will also test the hypothesis that adenosinergic tone is disrupted following adolescent social isolation, a model of early life stress that engenders increases in anxiety-like behavior as well as increases in ethanol consumption. Building upon this aim, Aim 2 will use behavioral assays to determine the ability of ADO, delivered directly into the BLA, to attenuate the increases in anxiety-like behavior and ethanol consumption brought on by social isolation. These studies will significantly advance our understanding of ADO signaling in the BLA and possibly identify novel neural substrates linking early life stress and increased anxiety-like behaviors and ethanol drinking. Moreover, insights gathered from these investigations may reveal promising new targets for development of novel pharmacotherapeutics for treating addiction and anxiety disorders.

描述（由申请人提供）：此申请为Ruth L. Kirschstein NRSA个人博士前奖学金，由Andrew R. Rau提交，目的是在Wake Forest大学健康科学系生理与药理学博士Jeff L. Weiner的指导下寻求研究培训资金。韦纳博士实验室的研究重点是揭示乙醇和焦虑相关疾病对突触和行为产生复杂影响的机制。本应用程序中提出的研究旨在首次表征腺苷的作用