Gene Delivery and Addiction

Harvey, Brandon

Abstract

In collaboration with Dr. Pietro Sanna (Scripps Institute) and Dr. Marisela Morales (NIDA), we provided our well-characterized AAV vector expressing the neurotrophic factor GDNF to help demonstrate that syndecan-3 limits cocaine intake by modulating effects of GDNF. This work has been published in Nature Communications. In collaboration with Dr. Woody Hopf (Gallo Institute) and Dr. Antonello Bonci (NIDA) we generated AAV vectors to modulate expression of NMDARs in the nucleus accumbens of the rat brain. Through this work, a mechanism of NMDAR contribution to altered neuronal circuits involved in aversion-resistant intake to alcohol was described. This work has been published in Nature Neuroscience. Our lab participated in a study led by Drs. Hope, Calu and Shaham (NIDA) that examined the contribution of the medial prefrontal cortex (PFC) in stress-induced reinstatement of palatable food seeking behavior in rats. We demonstrated that intracranial light delivery to rat PFC does not significantly affect expression of markers of glial activation. Overall, the study used an optogenetic approach to show that inhibition of neural activity in the rat mPFC alters stress-induced relase to food seeking in female rats. This work has been published in Journal of Neuroscience. We have 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 revision. re.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute on Drug Abuse (NIDA)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIADA000526-07
• Application #: 8933835
• Support Year: 7
• Fiscal Year: 2014

Institution

• Name: National Institute on Drug Abuse

Publications

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

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

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