EEG ANALYSIS OF DRUG REINFORCEMENT AND DEPENDENCE

内源性阿片系统在维持水平中起着重要作用 唤醒和睡眠-觉醒节律。这些机制还涉及到 阿片类药物和其他类别的滥用物质作为 自我管理行为的增强剂。 这个项目的总体目标是使用定量分析 脑电(EEG)研究阿片类药物的作用机制 对觉醒和睡眠-觉醒周期的影响，以及这些影响之间的关系 伤害性感受和强化的行为测量。计算机化 将使用定量脑电分析方法来表征药物 警觉、自由活动大鼠的依赖和自我管理。药效 无论是静脉注射还是静脉注射，都会观察到效果 慢性阻塞性肺疾病动物的脑室内输液 用于脑电记录的皮质电极。 在初步研究中，低剂量的阿片激动剂吗啡 显示出产生警觉的脑电模式，几乎没有慢波活动。 这被描述为不同步的脑电，并通过减少反映出来 总光谱功率。阿片类拮抗剂纳洛酮治疗增加 脑电中的慢波活动量，导致更大的总 光谱能量。当一系列的吗啡注射是自我注射时 作为一种增强剂，脑电总频谱能量的减少出现了更大的 比被动接受相同图案的受试者 输液。 建议在以下领域开展更多研究： L。阿片受体选择性。术后脑电的去同步化 小剂量阿片类激动剂的治疗是中央调节的，通过 MU阿片受体，具有参与胆碱能机制。 2.加固。在海马区产生的Theta节律将是 与阿片类药物强化作用有关。脑电活动与吗啡自身的相关性 管理将与质量不同的增强剂进行比较。 3.伤害性感受。吗啡自我催促过程中脑电活动的定量变化 给药将与药物前的伤害性水平和 对阿片类药物阻断的反应性。

The endogenous opioid system plays an important role in maintaining level of arousal and sleep-wake rhythms. These mechanisms are also involved in the ability of opioids and other classes of abused substances to act as reinforcers for self-administration behavior. The overall goal of this project is to use quantitative analysis of the electroencephalogram (EEG) to explore the mechanisms underlying opioid effects on arousal and the sleep-wake cycle, and to relate these effects to behavioral measures of nociception and reinforcement. Computerized methods for quantitative EEG analysis will be used to characterize drug dependence and self-administration in alert, freely-moving rats. Drug effects will be observed after either intravenous or intracerebroventricular infusions, in animals maintained with chronic cortical electrodes for EEG recording. In preliminary studies, low doses of the opioid agonist morphine have been shown to produce an alert EEG pattern with little slow wave activity.' This is described as a desynchronized EEG, and is reflected by reduced total spectral power. Treatment with opioid antagonist naloxone increases the amount of slow wave activity in the EEG, resulting in greater total spectral power. When a series of morphine infusions are self-administered as a reinforcer, reductions in EEG total spectral power occur to a greater extent than in subjects that passively receive the same pattern of infusions. Additional research is proposed in the following areas: l. Opioid Receptor Selectivity. Desynchronization of the EEG after treatment with low doses of opioid agonists is centrally mediated, through mu opioid receptors, with participation of cholinergic mechanisms. 2. Reinforcement. Theta rhythms generated in the hippocampus will be related to opioid reinforcing effects. EEC correlates of morphine self- administration will be compared with qualitatively different reinforcers. 3. Nociception. Quantitative EEC changes during morphine self- administration will be related to predrug levels of nociception and responsiveness to opioid blockade.