BEHAVIOR AND MECHANISM IN ACUTE AMPHETAMINE WITHDRAWAL

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 大鼠在接受中等剂量的安非他明20小时后活动不足。这种低活动度可能表明存在急性戒断状态和轻度抑郁。本研究的目的是建立一种急性戒断的动物模型，并利用它来研究戒断的机制和治疗方法。方法：研究方法。在过去的一年里，我们继续开发行为程序，旨在为苯丙胺治疗后20小时出现急性戒断提供一致的证据：我们评估了安非他明治疗后不同时间为食物工作(食欲行为)和消费食物(消费行为)。为了评估苯丙胺是否通过最初激活多巴胺受体而产生更长期的低活性，我们继续观察多巴胺受体拮抗剂预处理阻断苯丙胺诱导的低活性的能力。为了确定可能介导苯丙胺效应的分子事件，我们使用实时荧光定量聚合酶链式反应来观察治疗后不同时间几个脑区基因表达的变化(前强啡肽、D_1受体、D_2受体)。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Rats are hypoactive 20 hours after receiving a moderate dose of amphetamine. This hypo-activity may indicate the presence of an acute withdrawal state and of a low-grade depression. The purpose of the research is to develop an animal model of acute withdrawal and to use it to investigate mechanisms and treatments. Methods. In the past year we have continued to develop behavioral procedures designed to provide converging evidence for the presence of acute withdrawal 20 hours after amphetamine treatment: We assessed working for food (appetitive behavior) and consuming food (consummatory behavior) at different times following amphetamine treatment. In order to evaluate whether amphetamine produces longer-term hypoactivity by initially activating dopamine receptors, we continued to look at the ability of pre-treatment with dopamine receptor antagonists to block amphetamine-induced hypoactivity. In order to identify molecular events that might mediate amphetamine's effects, we used real-time PCR to look at changes in gene expression (prodynorphin, D1 receptor, D2 receptor) in several brain regions at different times following treatment.