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
Kuo, Chi-Chung; Shen, Hui; Harvey, Brandon K et al. (2016) Differential modulation of methamphetamine-mediated behavioral sensitization by overexpression of Mu opioid receptors in nucleus accumbens and ventral tegmental area. Psychopharmacology (Berl) 233:661-72
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Lee, Chun-Ting; Chen, Jia; Kindberg, Abigail A et al. (2016) CYP3A5 Mediates Effects of Cocaine on Human Neocorticogenesis: Studies using an In Vitro 3D Self-Organized hPSC Model with a Single Cortex-Like Unit. Neuropsychopharmacology :
Lee, Chun-Ting; Bendriem, Raphael M; Kindberg, Abigail A et al. (2015) Functional consequences of 17q21.31/WNT3-WNT9B amplification in hPSCs with respect to neural differentiation. Cell Rep 10:616-32
Henriksson, Richard; Bäckman, Cristina M; Harvey, Brandon K et al. (2014) PDYN, a gene implicated in brain/mental disorders, is targeted by REST in the adult human brain. Biochim Biophys Acta 1839:1226-32
Yu, Seong-Jin; Wu, Kou-Jen; Bae, Eun K et al. (2014) Methamphetamine induces a rapid increase of intracellular Ca(++) levels in neurons overexpressing GCaMP5. Addict Biol :
McDevitt, Ross A; Tiran-Cappello, Alix; Shen, Hui et al. (2014) Serotonergic versus nonserotonergic dorsal raphe projection neurons: differential participation in reward circuitry. Cell Rep 8:1857-69
Luo, Yu; Shen, Hui; Liu, Hua-Shan et al. (2013) CART peptide induces neuroregeneration in stroke rats. J Cereb Blood Flow Metab 33:300-10
Seif, Taban; Chang, Shao-Ju; Simms, Jeffrey A et al. (2013) Cortical activation of accumbens hyperpolarization-active NMDARs mediates aversion-resistant alcohol intake. Nat Neurosci 16:1094-100

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