Project 2 - Herbal Remedies to Prevent Alcohol Relapse in Animal Models

项目 2 - 在动物模型中预防酒精复吸的草药疗法

• 批准号: 6883594
• 负责人: DAVID H OVERSTREET
• 金额: $ 10.39万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-10-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6883594
• 关键词: Chinese; alcoholic beverage consumption; alcoholism /alcohol abuse; alcoholism /alcohol abuse chemotherapy; alternative medicine; behavior test; behavioral /social science research tag; cocaine; craving; cues; drug /alcohol abstinence; drug abuse chemotherapy; drug screening /evaluation; folk medicine; laboratory mouse; laboratory rat; nonhuman therapy evaluation; plant extracts; psychopharmacology; relapse /recurrence; substance abuse related behavior; substance abuse related disorder

Chinese herbal medicines have been used historically in the treatment of alcohol and drug abuse. They are still prescribed in China and Southeast Asia, and their efficacy has been documented. We have shown that one of these remedies, NPI-028, will reduce alcohol intake in alcohol-preferring rats and monkeys. The goal of this Research Project 2 is to determine the efficacy of herbal remedies (NPI-028 and NPI-025) and fractions in animal models of craving and relapse. First we will test the remedies and compounds derived from Project 1 with kappa activity for efficacy in reducing voluntary alcohol intake in alcohol-preferring C57Bl mice (Aim 1). Because of its small size, this species will require only a small amount of compound. Any compound that reduces alcohol intake in mice will be tested for effects on the elevated alcohol intake associated with alcohol deprivation in P rats (Aim 2). This elevated intake is reminiscent of the binge drinking exhibited by the alcoholic upon resuming drinking. Compound will be administered either shortly before resumption of drinking to examine acute effects or during abstinence (deprivation) to examine long-term effects on relapse. In Aim 3, effects on the reinstatement of responding for alcohol will be determined. This protocol also involves a period of abstinence, so it will be possible to administer compound either during the abstinence phase or acutely just before reinstatement. Aim 4 will test for effects on cocaine discrimination in rats and monkeys to address the potential for treatment of cocaine addiction. Aims 1-3 will be carried out at the Center for Alcohol Study, University of North Carolina, and Aim 4 will be performed at McLean Hospital/Harvard Medical School. We believe that only those herbal remedies or compounds that withstand rigorous tests in sequential animal models are worthy of clinical trials designed to prevent relapse in alcohol and drug addiction.

中草药历史上一直用于治疗酒精和药物滥用。它们在中国和东南亚仍然被使用，并且其功效已被记录。我们已经证明，其中一种药物 NPI-028 可以减少嗜酒大鼠和猴子的酒精摄入量。该研究项目 2 的目标是确定草药（NPI-028 和 NPI-025）及其成分在渴望和复发的动物模型中的功效。首先，我们将测试源自项目 1 的具有 kappa 活性的药物和化合物在减少嗜酒 C57Bl 小鼠自愿饮酒方面的功效（目标 1）。由于其体积小，该物种仅需要少量的化合物。 任何能减少小鼠酒精摄入量的化合物都将在 P 大鼠中测试其对与戒酒相关的酒精摄入量增加的影响（目标 2）。这种摄入量的增加让人想起酗酒者恢复饮酒后表现出的暴饮暴食。将在恢复饮酒前不久施用化合物以检查急性影响，或在戒酒（剥夺）期间施用化合物以检查对复发的长期影响。在目标 3 中，将确定对恢复酒精反应的影响。该方案还涉及一段禁欲期，因此可以在禁欲阶段或在恢复之前立即施用化合物。目标 4 将测试大鼠和猴子对可卡因辨别的影响，以解决可卡因成瘾的治疗潜力。目标 1-3 将 Aim 4 将在北卡罗来纳大学酒精研究中心进行，而 Aim 4 将在麦克莱恩医院/哈佛医学院进行。我们相信，只有那些在连续动物模型中经受住严格测试的草药或化合物才值得进行旨在预防酒精和药物成瘾复发的临床试验。