Mechanisms Mediating Cocaine Abuse in Socially Housed Female and Male Monkeys

这项受资助的研究项目现已进入第13个年头，旨在了解可卡因滥用的神经生物学。 在一种独特的非人灵长类动物模型中：社交场所中的静脉注射可卡因自我给药(SA) 食蟹猴。科学前提是，不同的机制维持可卡因SA基于社会 为了在这些群体中产生积极的结果，需要等级和性别，因此需要不同的药物治疗。 对于这一行政副刊，我们建议扩展社会的表型特征 饲养雌性和雄性猴子，包括睡眠指标。可卡因引起的睡眠时间改变， 架构和质量可能会影响认知过程，从而帮助人们避免继续 可卡因的使用。关于可卡因引起的睡眠障碍之间的关系，知识上存在差距 和认知表现，以及这些如何影响治疗结果。我们有一个独特的机会来研究 可卡因与睡眠的相互作用，因为我们目前有可卡因天真的社交场所，女性和男性 食蟹猴(n=4/性别)在不同的认知任务下接受训练。我们打算把它们植入 使用遥测设备记录脑电(EEG)活动，以评估睡眠/清醒状态 可卡因--幼稚的可卡因和之后的可卡因SA。在目标1中，我们将考察认知和 可卡因天真的群居雄性和雌性食蟹猴的睡眠/觉醒结构。每只猴子 目前正在接受四项认知任务的培训，这些任务使用剑桥大学的 神经心理测试和电池(CANTAB)仪器。在植入遥测设备记录脑电后 从在家中自由活动的猴子的笼子里，我们将检查每种动物的睡眠-唤醒体系结构 它与他们的社会等级有关；这些数据将作为检查可卡因SA在AIM中的影响的基线 2.我们假设了性别、月经周期和社会等级在睡眠结构上的差异，并认为猴子 (女性和男性)睡眠周期受干扰较少的人会有更好的认知特征。目标2中的研究 将第一个确定获得可卡因SA对社交场所睡眠结构的影响 猴子。我们假设，主要的雌性和从属的雄性将以比 当习得发生时，睡眠和认知会被打乱。在目标3中，我们建议 观察可卡因剂量(生理盐水，0.01-0.3 mg/kg/次注射)对睡眠结构的影响。我们建议给 猴子每天接触高剂量的可卡因，以确定耐受性是否发展到对睡眠的影响。 最后，我们将研究可卡因戒断对睡眠/觉醒结构的影响。我们假设睡眠， 脑电波检查对可卡因戒断敏感，提供了可卡因戒断的证据 动物模型中的症状。未来的研究将研究药物治疗如何影响睡眠/觉醒结构 在可卡因戒断期间和在再次接触可卡因之后，对认知的影响。将我们的研究扩展到 将睡眠包括在内也为未来药物治疗的评估提供了理由。

This funded research project, now in its 13th year, is aimed at understanding the neurobiology of cocaine abuse in a unique nonhuman primate model: intravenous cocaine self-administration (SA) in socially housed cynomolgus monkeys. The scientific premise is that different mechanisms maintain cocaine SA based on social rank and sex and thus different drug treatments will be required to produce a positive outcome in these groups. For this Administrative Supplement, we are proposing to extend the phenotypic characteristics of socially housed female and male monkeys to include measures of sleep. Cocaine-induced changes in sleep duration, architecture and quality could impact cognitive processes that would aid someone in refraining from continuing cocaine use. There is a gap in knowledge related to the relationship between cocaine-induced sleep disruptions and cognitive performance and how those affect treatment outcomes. We have a unique opportunity to study cocaine-sleep interactions because we currently have cocaine-naïve socially housed female and male cynomolgus monkeys (n=4/sex) being trained under various cognitive tasks. We propose to implant them with telemetry devices to record electroencephalographic (EEG) activity to assess sleep/wake states while cocaine-naïve and following cocaine SA. In Aim 1, we will examine the relationship between cognition and sleep/wake architecture in cocaine-naive socially housed male and female cynomolgus macaques. Each monkey is currently being trained on four cognitive tasks that assess different cognitive domains using the Cambridge Neuropsychological Test and Battery (CANTAB) apparatus. After implanting telemetry devices to record EEG from freely-moving monkeys within their home cage, we will examine each animal’s sleep-wake architecture as it relates to their social rank; these data will serve as a baseline for examining the effects of cocaine SA in Aim 2. We hypothesize sex, menstrual cycle and social rank differences in sleep architecture and that monkeys (females and males) with a less disrupted sleep cycle will have better cognitive profiles. The studies in Aim 2 will be the first to determine the effects of acquisition of cocaine SA on sleep architecture in socially housed monkeys. We hypothesize that dominant females and subordinate males will acquire at lower doses than the other monkeys and that when acquisition occurs, sleep and cognition will be disrupted. In Aim 3, we propose to examine the effects of cocaine dose (saline, 0.01-0.3 mg/kg/injection) on sleep architecture. We propose to give monkeys access to high cocaine doses daily, in order to determine if tolerance develops to the effects on sleep. Finally, we will examine the effects of cocaine abstinence on sleep/wake architecture. We hypothesize that sleep, as assessed with EEG, will be sensitive to cocaine abstinence, providing evidence of cocaine withdrawal symptoms in an animal model. Future studies will examine how drug treatments affect sleep/wake architecture and cognition, during cocaine abstinence and following re-exposure to cocaine. Expanding our research to include sleep also provides rationale for the evaluation of future drug treatments.