Chronic Ethanol Consumption, Opioids and Dopamine

慢性乙醇消耗、阿片类药物和多巴胺

• 批准号: 7168858
• 负责人: Brendan M Walker
• 金额: $ 4.88万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-07 至 2007-01-06
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7168858
• 关键词: alcoholism /alcohol abuse; amygdala; behavior test; dopamine; drug habituation; drug withdrawal; endogenous opioid; laboratory rat; neurochemistry; operant conditionings; opioid receptor; pharmacokinetics; postdoctoral investigator; psychopharmacology; reinforcer

DESCRIPTION (provided by applicant): Due to evidence suggesting that brain reinforcement systems are engaging in allostatic processes to combat the chronic effects of ethanol administration, the present series of experiments are designed to identify changes in basal and ethanol administration-contingent endogenous opioid and dopamine levels in the rat brain during acute and protracted withdrawal in ethanol dependent and non-dependent animals. Furthermore, non-selective and selective opioid receptor antagonists/agonists will be used to pharmacologically study the role of opioids within specific regions of the extended amygdala during acute withdrawal in ethanol dependent and non-dependent rats. These series of experiments will help to classify allostatic changes in brain reinforement systems that could contribute to addiction and dependence and possibly help to identify appropriate pharmacotherapeutics for use in the treatment of alcoholism.

描述（由申请人提供）：由于证据表明大脑强化系统正在参与调节过程以对抗乙醇施用的慢性影响，因此本系列实验旨在确定基础和乙醇施用相关的内源性阿片类药物和多巴胺的变化乙醇依赖和非依赖动物急性和长期戒断期间大鼠大脑中的水平。 此外，非选择性和选择性阿片受体拮抗剂/激动剂将用于药理学研究阿片类药物在乙醇依赖和非依赖大鼠急性戒断期间在扩展杏仁核特定区域内的作用。这一系列的实验将有助于对大脑强化系统中可能导致成瘾和依赖的变稳态变化进行分类，并可能有助于确定用于治疗酒精中毒的适当药物治疗方法。

项目成果

The gamma-aminobutyric acid-B receptor agonist baclofen attenuates responding for ethanol in ethanol-dependent rats.

γ-氨基丁酸-B 受体激动剂巴氯芬可减弱乙醇依赖大鼠对乙醇的反应。

• 发表时间: 2007-01
• 作者: Walker, Brendan M;Koob, George F
• 通讯作者: Koob, George F

alpha1-noradrenergic receptor antagonism blocks dependence-induced increases in responding for ethanol.

α1-去甲肾上腺素能受体拮抗作用可阻断依赖性诱导的乙醇反应增加。

• 发表时间: 2008-03
• 作者: Walker, Brendan M;Rasmussen, Dennis D;Raskind, Murray A;Koob, George F
• 通讯作者: Koob, George F

Pharmacological evidence for a motivational role of kappa-opioid systems in ethanol dependence.

卡帕阿片系统在乙醇依赖中的激励作用的药理学证据。

• 发表时间: 2008-02
• 作者: Walker, Brendan M;Koob, George F
• 通讯作者: Koob, George F

Regarding "Dynorphin is a downstream effector of striatal BDNF regulation of ethanol intake".

关于“强啡肽是纹状体 BDNF 调节乙醇摄入量的下游效应器”。

• 发表时间: 2008-07
• 作者: Walker, Brendan M;Koob, George F
• 通讯作者: Koob, George F