Role of Circadian Entrainment in Drug Intake and Abuse

昼夜节律牵引在药物摄入和滥用中的作用

• 批准号: 7122822
• 负责人: ANN E KOSOBUD
• 金额: $ 29.19万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7122822
• 关键词: behavior test; behavioral /social science research tag; chordate locomotion; circadian rhythms; craving; cues; drug abuse; drug addiction; ethanol; fentanyl; haloperidol; laboratory rat; methamphetamine; motivation; nicotine; operant conditionings; reinforcer; stimulus interval; substance abuse related behavior

DESCRIPTION (provided by applicant): If a rat is given a single daily meal, over time it develops a pattern of locomotor activity that anticipates the meal, even under conditions that provide no time cues. This anticipatory activity has been attributed to a meal-entrained circadian rhythm. Administration of some abused drugs has been shown to have entraining effects that resemble those of meals. For example, rats given injections of methamphetamine (MA) every 24 h also develop increased locomotor activity 1-3 hr before injections, even under conditions that provide no time cues. Rats provided with meals, or given MA or cocaine injections on a schedule beyond the typical range of circadian entrainment (S31 h), do not develop anticipatory activity, but do show a transient increase in locomotion that follows the meal or drug injection by 24-28 h. Meals also entrain a number of physiological rhythms, including release of corticosterone, enzyme activity in the intestines, pancreas and liver, mitotic activity in the intestinal epithelium, and insulin release. Together, these changes function to promote and prepare for the results of feeding behavior. The purpose of this research is to determine if drug-related circadian rhythms play a similar role in drug taking. Research on this topic is important because drug-entrained circadian rhythms could prime and prepare organisms for daily episodes of drug taking, enhancing search behavior, intake, and tolerance. Such rhythms could also contribute to drug-motivation and relapse in an abstinent person otherwise actively avoiding priming cues such as people, places or objects associated with past drug use. If this is the case, treatment strategies that consider circadian effects in designing pharmacological and behavioral interventions should have improved success. In the experiments proposed here, the potential role of drug-related circadian rhythms in drug abuse will be explored in three aims. Aim1 tests the hypothesis that circadian entrainment is typical of and limited to drugs of abuse, by screening 4 abused drugs (methamphetamine, fentanyl, nicotine and ethanol) and 2 control drugs (haloperidol, p-hydroxyamphetamine) for their ability to entrain locomotor activity. Aim 2 addresses whether circadian anticipatory activity is related to drug seeking and intake. Aim 3 tests whether drug intake and reinforcement are increased when drugs are available on a circadian schedule, compared to a non-circadian schedule. Taken together, these experiments will establish whether circadian entrainment is a common property of abused drugs, and its importance in the regulation of drug-seeking and taking.

描述（由申请人提供）：如果给大鼠每日一顿饭，随着时间的流逝，它会产生一种运动活动的模式，即使在没有时间提示的条件下，也可以预见餐点。这种预期活动归因于饮食中的昼夜节律。某些滥用药物的给药已显示出具有类似餐食的诱因。例如，每24小时注射甲基苯丙胺（MA）的大鼠也会在注射前1-3小时出现运动活性增加，即使在没有时间提示的条件下也是如此。在典型的圆形夹带（S31 h）之外，以餐食或可卡因注射的大鼠为食品或可卡因注射（S31小时）不会发展预期活动，但确实显示出24-28小时的饮食或药物注射后运动的瞬时增加。餐食还包括许多生理节奏，包括释放皮质酮，肠中的酶活性，胰腺和肝脏，肠上皮上皮中的有丝分裂活性以及胰岛素释放。这些变化共同促进和准备喂养行为的结果。这项研究的目的是确定与药物相关的昼夜节律在药物服用中是否起类似的作用。对该主题的研究很重要，因为被药物输入的昼夜节律可以使生物每天服用，增强搜索行为，摄入量和耐受性。这种节奏也可能有助于戒毒者的吸毒和复发，否则会积极避免启动提示，例如与过去使用毒品相关的人，地方或物体。如果是这种情况，那么考虑昼夜节律在设计药理和行为干预措施方面的效果的治疗策略应改善成功。在此处提出的实验中，将在三个目标中探讨与药物有关的昼夜节律在药物滥用中的潜在作用。 AIM1检验了一个假设，即昼夜节律夹带是典型的，并且仅限于滥用药物，通过筛选4种滥用药物（甲基苯丙胺，芬太尼，烟碱和乙醇）和2种对照药物（Haloperidol，p-羟基苯丙胺），以便其能够发挥作用。 AIM 2解决了昼夜节律预期活动是否与寻求药物和摄入有关。 AIM 3测试与非周期时间表相比，当昼夜节律计划可用药物时，药物摄入和增强是否会增加。综上所述，这些实验将确定昼夜节律是否是滥用毒品的共同特性及其在监管毒品和服用中的重要性。