EEG ANALYSIS OF DRUG REINFORCEMENT AND DEPENDENCE

内源性阿片系统在维持脑内阿片受体水平中起重要作用 唤醒和睡眠-觉醒节律的变化。 这些机制也参与了 阿片类药物和其他类别的滥用物质的能力， 自我管理行为的监督者。 本项目的总体目标是使用定量分析， 脑电图（EEG），以探讨阿片类药物的机制 影响觉醒和睡眠-觉醒周期，并将这些影响 伤害感受和强化的行为测量。 计算机化 定量EEG分析方法将用于表征药物 依赖性和自我管理的警觉，自由移动的大鼠。 药物 将在静脉内或静脉内注射后观察效果。 脑室内输注，在维持慢性 皮层电极记录脑电图 在初步研究中，低剂量的阿片类激动剂吗啡已经被用于 显示出产生具有很少慢波活动的警报EEG模式。' 这被描述为去干扰化的EEG，并且通过减少的 总光谱功率 阿片类拮抗剂纳洛酮治疗增加 脑电图中慢波活动的数量，导致更大的总 光谱功率 当一系列的吗啡注射是自我管理的时候 作为一种替代品，EEG总频谱功率的降低发生在更大的范围内， 比被动接受相同模式的受试者的程度 输液 建议在以下领域开展进一步研究： L.阿片受体选择性。 脑电去噪后 用低剂量阿片激动剂治疗是中枢介导的，通过 μ阿片受体，参与胆碱能机制。 2.加固. 海马体中产生的θ节律 与阿片类药物的强化作用有关 吗啡自身的EEC相关物 将给药与定性不同的赋形剂进行比较。 3.伤害感受。 吗啡自身给药过程中脑电图的定量变化 给药将与伤害感受的给药前水平相关， 对阿片类药物阻断的反应。

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.