CIRCADIAN PATTERNS OF BEHAVIOR AND GENE EXPRESSION FOLLOWING ?RECREATIONAL? OR ?

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 这项研究的目的是比较“娱乐性”吸毒模式和导致滥用的模式所产生的行为和基因表达变化。我们的研究对象都是老鼠。对于行为工作，每只动物都将被连续地关在一个有12-12小时明暗周期的站点中，并配备提供食物和水的设备。将全天24小时监测食物摄入量。一组动物将被暴露在一种模拟娱乐用药的制度下：它们将每隔五天接受中等剂量但无毒的苯丙胺(2.0 mg/kg)。服用该剂量后18-26小时会出现短暂的停药状态或“宿醉”，特征是活动不足和食物摄入量减少。另一组动物将面临不断升级的安非他明“狂欢”模式。在食物摄入量稳定后，将进行为期五天的测试。在试验的第一天，动物将接受生理盐水注射，在第三天，它们将接受2.0毫克/公斤的苯丙胺的“挑战”注射。狂欢制度产生的食物摄取的昼夜模式将与娱乐性吸毒制度产生的食物摄取的昼夜模式进行比较。在基因表达工作中，大鼠将被安置在橱柜中的单独浴缸中，它们将根据刚刚为行为研究描述的时间表接受娱乐或狂欢的苯丙胺和测试。我们将评估与多巴胺、谷氨酸和GABA受体相关的基因在伏隔核、背侧纹状体和额叶皮质的表达，有时与精神运动刺激状态(治疗后1-6小时)和娱乐药物使用期间观察到的短暂戒断状态相对应。INBRE提供资金支持一名将进行这项研究的个人。到目前为止，该个体已经接受了将在研究中使用的一些行为和药理学程序的培训。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal of the research is to compare behavioral and gene expression changes produced by a "recreational" pattern of drug use and by a pattern entailing abuse. Our subjects are rats. For the behavioral work, each animal will be continuously housed in a station with a 12-12 hour light-dark cycle and devices for providing food and water. Food intake will be monitored 24 hours a day. One group of animals will be exposed to a regime that mimics recreational drug use: They will receive a moderately high but non-toxic dose of amphetamine (2.0 mg/kg) at five-day intervals. A transient withdrawal state or "hangover," characterized by hypo-activity and reduced food intake occurs 18-26 hours after this dose. Another group of animals will be exposed to an escalating "binge" pattern of amphetamine administration. After food intake stabilizes, five-day tests will be run. On test day 1, animals will receive a saline administration, and on day 3 they will receive a "challenge" administration of 2.0 mg/kg amphetamine. Circadian patterns of food intake produced by the binge regime will be compared to those produced by a recreational drug use regime. For the gene expression work, rats will be housed in individual tubs in cabinets, and they will receive recreational or binge amphetamine and tests according to the schedule just described for the behavioral studies. We will assess expression for genes related to dopamine, glutamate and GABA receptors, in nucleus accumbens, dorsal striatum, and frontal cortex, at times corresponding to the psychomotor stimulant state (hour 1-6 post-treatment) and the transient withdrawal state observed during the recreational drug use regime. INBRE provided funding to support an individual who will conduct this research. So far the individual has received training on some of the behavioral and pharmacological procedures that will be employed in the study.