Structural Brain Mapping of Cocaine Action

拟议的工作是NIDA东查尔斯敦MGH项目的一部分。初步研究表明，通过功能性磁共振成像（fMRI）测量的可卡因引起的区域脑血容量（rCBV）变化，在有可卡因自我给药史的大鼠中比在未给药动物（即在食物强化行为中表现相同时间的大鼠）中更持久。本研究的目的是验证慢性动物的这种持续反应与慢性动物边缘结构中多巴胺释放的幅度和持续时间的增加有关的假设。第二个目标是检验不同模式的rCBV变化将与多巴胺D1 （SKF 81297, SKF 38393）和D2 （7-OH DPAT）受体激动剂给药有关的假设。最后，该假设将被评估，非选择性5-羟色胺（5-HT）受体拮抗剂（甲氧thepin）和选择性5-羟色胺/1b/d部分激动剂（GR 127935）单独或与可卡因联合使用会对慢性和幼稚大鼠的rCBV产生明显改变。这些动物将在波士顿大学医学院行为药理学实验室进行准备和训练，然后被运送到查尔斯顿- mgh实验室的功能磁共振成像实验室。与其他成像技术相比，使用功能磁共振成像测量rCBV提供了更好的药物诱导变化的时间分辨率。本研究的结果将有助于确定慢性可卡因自我给药如何随时间改变区域脑功能的多巴胺能和血清素能机制。

The proposed work is part of the MGH, East Charlestown Program Project to the NIDA. Preliminary research has shown that cocaine induced changes in regional cerebral blood volume (rCBV), as measured by functional magnetic resonance imaging (fMRI), are more sustained in rats with a history of cocaine self-administration than in drug naive animals (i.e. rats that have performed for an equal amount of time on a food-reinforced behavior). The purpose of the investigation proposed here is to test the hypothesis that this sustained response in chronic animals correlates with an increase in the magnitude and duration of dopamine release in limbic structures of chronic animals. A second goal is to examine the hypotheses that different patterns of change in rCBV will be associated with the administration of dopamine D1 (SKF 81297, SKF 38393) and D2 (7-OH DPAT) receptor agonists to chronic as compared to naive animals. Finally, the hypothesis will be assessed that administration of non-selective serotonin (5-HT) receptor antagonists (methiothepin) and of selective 5-HT/1b/d partial agonists (GR 127935) alone and in combination with cocaine will produce distinct alterations in rCBV in chronic and naive rats. The animals will be prepared and trained at the laboratory of Behavioral Pharmacology, BU School of Medicine and then transported to the fMRI Laboratory at the Charlestown-MGH Laboratories. Use of fMRI measures of rCBV provides better time resolution of drug induced changes than do other imaging techniques. The results of this study will help to establish how chronic cocaine self- administration alters regulation by dopaminergic and serotonergic mechanisms of regional brain function over time.