Gene Delivery and Addiction

我们产生了表达人μ阿片受体（huMOR）的AAV载体，并且正在评估huMOR在小鼠中甲基苯丙胺致敏中的作用。 我们的初步研究结果表明，通过AAV载体在特定脑区域中表达huMOR改变了甲基苯丙胺的致敏性。 我们已经提交了这项工作的出版，目前正在审查中。 我们还产生了表达谷氨酸转运蛋白（GLT-1）的AAV载体，并证明其功能。 我们正在使用大鼠中风模型研究GLT-1减少缺血引起的损伤的能力。 通过微透析测量，对缺血的保护伴随着缺血诱导的谷氨酸溢出的减少，这项研究于今年发表。 产生AAV-GLT-1以调节细胞外谷氨酸的水平。 我们已经开始实验检查通过AAV过量GLT-1过表达降低谷氨酸兴奋毒性的能力。 我们也开始研究特定脑区GLT-1过表达对甲基苯丙胺致敏的影响。 这些实验正在进行中。 最后，我们与布鲁斯霍普博士（NIDA IRP）合作开发了使用FACS从啮齿动物脑中分离神经元的测定法，以了解可卡因暴露后细胞特异性诱导的变化。

We generated an AAV vector expressing the human mu opioid receptor (huMOR) and are evaluating the role of huMOR in methamphetamine sensitization in mice. Our preliminary findings show that huMOR expression by an AAV vector in specific brain regions alters methamphetamine sensitization. We have submitted this work for publication and it is currently under review. We have also generated an AAV vector expressing the glutamate transporter (GLT-1) and demonstrated that it functional. We have ongoing work examining the ability of GLT-1 to reduce damage caused by ischemia using a rat model of stroke. The protection against ischemia was accompanied by a decrease in ischemia-induced glutamate overflow as measured by microdialysis and this study was published this year. AAV-GLT-1 was created to modulate the levels of extracellular glutamate. We have begun experiments examining the ability of excess GLT-1 overexpression by AAV to reduce excitoxicity by glutamate. We have also begun examining the GLT-1 overexpression in specfic brain regions for alterations to methamphetamine sensitization. These experiments are ongoing. Lastly, we collaborated with Dr. Bruce Hope (NIDA IRP) to the development of assay to isolate neurons from rodent brain using FACS to understand the cell-specific induced changes following cocaine exposure.