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.

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2013
Total Cost
$33,797
Indirect Cost
Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
Zip Code
Harvey, Brandon K; Chou, Jenny; Shen, Hui et al. (2009) Diadenosine tetraphosphate reduces toxicity caused by high-dose methamphetamine administration. Neurotoxicology 30:436-44
Shen, Hui; Luo, Yu; Kuo, Chi-Chung et al. (2009) 9-Cis-retinoic acid reduces ischemic brain injury in rodents via bone morphogenetic protein. J Neurosci Res 87:545-55
Lu, Lin; Wang, Xi; Wu, Ping et al. (2009) Role of ventral tegmental area glial cell line-derived neurotrophic factor in incubation of cocaine craving. Biol Psychiatry 66:137-45
Chou, J; Luo, Y; Kuo, C-C et al. (2008) Bone morphogenetic protein-7 reduces toxicity induced by high doses of methamphetamine in rodents. Neuroscience 151:92-103
Chou, J; Harvey, B K; Ebendal, T et al. (2008) Nigrostriatal alterations in bone morphogenetic protein receptor II dominant negative mice. Acta Neurochir Suppl 101:93-8
Shen, Hui; Luo, Yu; Kuo, Chi-Chung et al. (2008) BMP7 reduces synergistic injury induced by methamphetamine and ischemia in mouse brain. Neurosci Lett 442:15-8