Laboratory studies on oxytocin for treatment of alcohol dependence

催产素治疗酒精依赖的实验室研究

• 批准号: 8619250
• 负责人: GARY S WAND
• 金额: $ 19.17万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-15 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8619250
• 关键词: Abstinence; Acute; Adrenal Gland Hyperfunction; Adult; Alcohol consumption; Alcohol dependence; Alcohol withdrawal syndrome; Alcoholic beverage heavy drinker; Alcohols; Animal Model; Animals; Anxiety; Arithmetic; Attenuated; Benzodiazepines; Blood alcohol level measurement; Clinical; Clinical Trials; Consumption; Corticotropin-Releasing Hormone; Data; Disulfiram; Dopamine; Dose; Double-Blind Method; Drug Metabolic Detoxication; Drug Tolerance; Female; Foundations; Future; Goals; Gold; Heart Rate; Heavy Drinking; Hydrocortisone; Inpatients; Intranasal Administration; Laboratories; Laboratory Procedures; Laboratory Study; Link; Lorazepam; Measures; Memory; Moods; Motivation; Naltrexone; National Institute on Alcohol Abuse and Alcoholism; Neuropeptides; Oxytocin; Participant; Patients; Performance; Pharmaceutical Preparations; Physiological; Placebo Control; Placebos; Procedures; Process; Protocols documentation; Psyche structure; Psychological reinforcement; Public Speaking; Randomized; Relapse; Research; Rewards; Risk; Rodent Model; Role; Sample Size; Self Administration; Severities; Sex Characteristics; Stress; Symptoms; System; Time; Trier Social Stress Test; United States Food and Drug Administration; Withdrawal; Withdrawal Symptom; acamprosate; addiction; alcohol abuse therapy; alcohol craving; alcohol effect; alcohol misuse; alcohol reinforcement; alcohol relapse; alcohol related problem; alcohol reward; alcohol seeking behavior; alcohol sensitivity; alcohol use disorder; base; biological adaptation to stress; classical conditioning; clinical efficacy; craving; drinking; experience; human subject; hypothalamic-pituitary-adrenal axis; improved; interest; male; negative mood; pre-clinical; public health relevance; response; reward circuitry; social stress; stem; urinary

DESCRIPTION (provided by applicant): The goal of this R21 proposal is to provide the foundation for future research to examine the utility of the neuropeptide oxytocin (OT) as a new treatment for alcohol use disorders (AUD). Interest in OT as an alcohol treatment stems from its role in adaptive processes including reward, associative learning, memory, and stress responses. Support for its use is based on studies in animal models of addiction showing that OT reduced alcohol reinforcement, attenuated drug tolerance, and decreased withdrawal symptoms. OT exerts its effects via interactions with the hypothalamic-pituitary-adrenal (HPA) axis, as well as dopamine mesolimbic reward and corticotrophin-releasing factor (CRF) stress systems. OT effects on stress systems are of high interest given the strong link between stress, alcohol drinking and relapse, and known dysregulation of HPA-axis activity in heavy drinkers. Both preclinical and clinical evidence provide evidence that OT may help to normalize blunted stress responses, and attenuate alcohol withdrawal associated hypercortisolism, negative mood and withdrawal symptoms. Using gold-standard laboratory procedures in heavy drinkers, we will examine the effects of intranasal OT administration on cortisol stress responses and different measures predictive of alcohol use and misuse under double-blind placebo controlled conditions. Aim 1 will examine the effects of oxytocin on alcohol withdrawal, including symptom severity, alcohol craving, cortisol and negative mood. Aim 2 will examine the effects of oxytocin on response to social stress. Aim 3 will examine the effects of oxytocin on motivation to drink. Aim 4 will examine the effects of oxytocin on alcohol sensitivity. These preliminary data will provide critical information on the potential of OT as a treatment for alcohol drinking problems and will provide the basis for determination of sample sizes for future comprehensive research and clinical trials.

描述（由申请人提供）：该R21提案的目的是为将来的研究提供基础，以研究神经肽催产素（OT）作为酒精使用障碍的新方法（AUD）。对OT作为酒精治疗的兴趣源于其在适应过程中的作用，包括奖励，联想学习，记忆和压力反应。对其使用的支持是基于在成瘾动物模型中的研究，表明OT降低了酒精加强，减弱药物耐受性和戒断症状的降低。 OT通过与下丘脑 - 垂体 - 肾上腺（HPA）轴以及多巴胺中唇胶质奖励和皮质营养蛋白释放蛋白释放因子（CRF）应力系统的相互作用发挥作用。鉴于压力，饮酒和复发和已知的重饮酒中HPA轴活性失调之间的牢固联系，对压力系统的影响引起了人们的兴趣。临床前和临床证据都提供了证据，证明OT可能有助于使压力钝化的压力反应正常化，并减轻与酒精戒断相关的高皮质溶液，负面情绪和戒断症状。我们将使用金标准的实验室程序中的重饮酒者，我们将检查鼻内OT给药对皮质醇应激反应的影响以及在双盲安慰剂控制条件下可预测酒精使用和滥用饮酒的不同措施。 AIM 1将检查催产素对戒酒的影响，包括症状严重程度，渴望酒精，皮质醇和负面情绪。 AIM 2将检查催产素对社会压力反应的影响。 AIM 3将检查催产素对饮酒动机的影响。 AIM 4将检查催产素对酒精敏感性的影响。这些初步数据将提供有关OT作为饮酒问题的潜力的关键信息，并将为确定样本量的基础，以确定未来的全面研究和临床试验。