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
5
Fiscal Year
2012
Total Cost
$273,270
Indirect Cost
Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
Zip Code
Anttila, Jenni E; Albert, Katrina; Wires, Emily S et al. (2018) Post-stroke Intranasal (+)-Naloxone Delivery Reduces Microglial Activation and Improves Behavioral Recovery from Ischemic Injury. eNeuro 5:
Zallar, L J; Tunstall, B J; Richie, C T et al. (2018) Development and initial characterization of a novel ghrelin receptor CRISPR/Cas9 knockout wistar rat model. Int J Obes (Lond) :
Li, Xuan; Carreria, Maria B; Witonsky, Kailyn R et al. (2018) Role of Dorsal Striatum Histone Deacetylase 5 in Incubation of Methamphetamine Craving. Biol Psychiatry 84:213-222
Wallace, Veronica J; Cimbro, Raffaello; Rubio, F Javier et al. (2017) Neurons Internalize Functionalized Micron-Sized Silicon Dioxide Microspheres. Cell Mol Neurobiol 37:1487-1499
Koskela, Maryna; Bäck, Susanne; Võikar, Vootele et al. (2017) Update of neurotrophic factors in neurobiology of addiction and future directions. Neurobiol Dis 97:189-200
Sharpe, Melissa J; Marchant, Nathan J; Whitaker, Leslie R et al. (2017) Lateral Hypothalamic GABAergic Neurons Encode Reward Predictions that Are Relayed to the Ventral Tegmental Area to Regulate Learning. Curr Biol 27:2089-2100.e5
Gomez, Juan L; Bonaventura, Jordi; Lesniak, Wojciech et al. (2017) Chemogenetics revealed: DREADD occupancy and activation via converted clozapine. Science 357:503-507
Wires, Emily S; Trychta, Kathleen A; Bäck, Susanne et al. (2017) High fat diet disrupts endoplasmic reticulum calcium homeostasis in the rat liver. J Hepatol 67:1009-1017
Wires, Emily S; Henderson, Mark J; Yan, Xiaokang et al. (2017) Longitudinal monitoring of Gaussia and Nano luciferase activities to concurrently assess ER calcium homeostasis and ER stress in vivo. PLoS One 12:e0175481
Richie, Christopher T; Whitaker, Leslie R; Whitaker, Keith W et al. (2017) Near-infrared fluorescent protein iRFP713 as a reporter protein for optogenetic vectors, a transgenic Cre-reporter rat, and other neuronal studies. J Neurosci Methods 284:1-14

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