MPHETAMINE-INDUCED ACUTE WITHDRAWALS/REVERSIBLE DEPRESSION IN RATS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。中剂量和高剂量的安非他明在给药20小时后会产生低活性。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。在过去的一年里，我们继续制定程序，为苯丙胺治疗20小时后出现急性戒断提供统一的证据。在安非他命注射后的不同时间，我们采用了累进比率和条件位置程序，以评估为报酬而工作的意愿，并推断当前内部状态的性质。为了确定产生较长时间的苯丙胺诱导的低活性所必需的短暂的多巴胺能变化，我们开始观察多巴胺受体拮抗剂预处理阻断苯丙胺诱导的效应的能力。为了开始鉴定介导苯丙胺诱导的低活性表达的分子变化，我们完成了一个小规模的？微阵列研究：生理盐水或苯丙胺处理20小时后，检测伏隔核基因表达。20小时后，服用安非他明支持条件性地点厌恶，当时可能存在厌恶的内心状态。安非他明还影响了在服药后的头24小时内在不同时间工作以换取报酬的意愿。微阵列结果确定了一些可能参与急性戒断表达的候选基因。结果与服用安非他明20小时后出现的急性戒断一致。已确定可能促进急性戒断发生的因素。这项研究可能会产生一种动物模型，可以用来研究急性戒断和轻度抑郁症。信息学中的问题。

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. Moderate and high doses of amphetamine produce hypo-activity 20 hours after they are administered. 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. In the past year we have continued to develop procedures designed to provide converging evidence for the presence of acute withdrawal 20 hours after amphetamine treatment. At different times following amphetamine administration, we have employed progressive ratio and conditioned place procedures, in order to assess willingness to work for reward and to infer the nature of the internal state present. In order to identify the short dopaminergic changes that might be necessary to produce longer term amphetamine-induced hypo-activity, we began to look at the ability of pre-treatment with dopamine receptor antagonists to block amphetamine induced effects. In order to begin to identify the molecular changes that mediate the proximate expression of amphetamine-induced hypo-activity, we completed a ?small scale? micro array study: Twenty hours after treatment with either saline or amphetamine, gene expression in the nucleus accumbens was assessed. Amphetamine administration supported a conditioned place aversion 20 hours later, and an aversive internal state may have been present at that time. Amphetamine also compromised willingness to work for reward at different times during the first 24 hours following administration. The micro-array results identified a number of candidate genes that might be involved in the expression of acute withdrawal. Results are consistent with the presence of acute withdrawal 20 hours after amphetamine administration. Factors that may promote the occurrence of acute withdrawal have been identified. The research may yield an animal model with which acute withdrawal and low grade depression can be studied. issues in informatics.