Ethanol: Protracted Changes in Brain Glucose Metabolism

描述(由申请人提供)： 对于酗酒者，即使在停止饮酒后，也可能会有持续数月甚至数年的残余影响。戒酒的人，由于各种原因，在喝完最后一杯酒后很久就会有饮酒的欲望。尽管有证据表明，在啮齿动物中长期服用乙醇会导致神经解剖损伤，并伴随认知障碍，但只有轻微的迹象表明，戒断后大脑局部代谢葡萄糖的利用可能会发生变化。虽然渴望通常被认为是线索所表现出来的，但线索引起的脑内变化的唯一动物实验模型一直局限于研究在多次重复酒精剂量的最后24小时后神经递质变化的测量。这项研究的具体目的是检验这样一种假设，即口服自我饮酒会导致大脑基础新陈代谢的长期变化，而且这些影响会因酒精线索的存在而增强。建议的实验将使用定量的2-脱氧-D-[I-14C]葡萄糖(2-DG)放射自显影方法来确定停止每日口服乙醇几周后Wistar大鼠大脑局部葡萄糖代谢率。这些影响将在存在和不存在与摄入乙醇相关的线索的情况下进行研究。2-DG分析将重点放在边缘系统的那些相互连接的区域，这些区域已经被证明是通过长期口服乙醇自我给药而改变的。积极的发现将有助于未来的研究，旨在了解这些持久效应所涉及的机制，并开发可能干扰这些作用的药物干预措施。

DESCRIPTION (provided by applicant): In the alcoholic, even after the cessation of drinking, there may be residual effects that last for months and possibly years. The abstinent alcoholic, for a variety of reasons, will have a craving for alcohol long after the last drink. Although there is evidence that chronic ethanol administration in rodents can cause neuroanatomical damage with concomitant cognitive deficits, there has been only a slight suggestion that there may be post-withdrawal changes in functional local cerebral metabolic glucose utilization. Although craving is generally believed to be cue manifested the only animal experimental models of cue induced intracerebral changes have been confined to the study of the measurement of neurotransmitter changes 24 hours after the last of a number of repeated ethanol doses. The specific aims of the research is to test the hypothesis that there are protracted changes in basal cerebral metabolism resulting from oral self- administration of alcohol and that these effects are enhanced by the presence of alcohol cues. The proposed experiments will use the quantitative 2-deoxy-D-[I- 14C]glucose (2-DG) autoradiographic method to determine the local cerebral metabolic rates of glucose a number of weeks after the cessation of daily oral self-administration of ethanol in the Wistar rat. These effects will be studied in the presence and absence of cues associated with the ingestion of the ethanol. The 2-DG analysis will focus on those interconnected regions of the limbic system that have been shown to be altered by chronic oral ethanol self- administration. Positive findings will allow for future research directed toward the understanding of the mechanisms involved in these protracted effects and the developments of possible pharmacological interventions that will interfere with these actions.