MPHETAMINE-INDUCED ACUTE WITHDRAWALS/REVERSIBLE DEPRESSION IN RATS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。中等和高剂量的安非他明在服用20小时后会产生活动减退。这种活动减退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，并利用它来研究机制和治疗方法。在过去一年中，我们继续制定程序，旨在提供安非他明治疗后20小时出现急性戒断的综合证据。在安非他明管理后的不同时间，我们采用了渐进的比例和条件的地方程序，以评估愿意为奖励工作，并推断目前的内部状态的性质。为了确定短期的多巴胺能变化，可能是必要的，以产生长期的安非他明诱导的活动减退，我们开始研究的能力，预处理与多巴胺受体拮抗剂阻断安非他明诱导的影响。为了开始，以确定介导的安非他明诱导的低活性的近似表达的分子变化，我们完成了一个？小规模？微阵列研究：在用盐水或安非他明处理后20小时，评估丘脑核中的基因表达。安非他明管理支持条件性的地方厌恶20小时后，和一个厌恶的内部状态可能已经存在于那个时候。安非他明还损害了在给药后24小时内不同时间为奖励而工作的意愿。微阵列结果鉴定了许多可能参与急性戒断表达的候选基因。结果与安非他明给药后20小时出现急性戒断一致。已经确定了可能促进急性戒断发生的因素。该研究可能会产生一种动物模型，用于研究急性戒断和轻度抑郁症。信息学的问题。

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.