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Dorit Ron, PhD

Dorit Ron, PhD
Associate Professor, Department of Neurology
Research Summary:
Molecular neurobiology of drug addiction

Harmful excessive use of drugs of abuse alcohol has a severe impact on society and is one of the major causes of morbidity and mortality in the population. My lab is interested in elucidating molecular neuroadaptations that occur in the adult brain in response to drugs of abuse and alcohol exposure. Our long-term goal is to identify novel targets that could potentially be developed as therapeutics to treat phenotypes associated with addiction including excessive, uncontrolled drug intake, drug seeking and relapse. To do so, we combine molecular, genetic, electrophysiological and behavioral paradigms in rodents to address the following questions:

  • What are the mechanisms that prevent the majority of social alcohol drinkers from developing alcohol abuse disorders?
  • Are there molecular factors that increase the vulnerability and propensity to develop drug of abuse-related disorders?
  • What are the signaling pathways that drive the transition from recreational use to uncontrolled drug intake regardless of negative consequences, and how can the transition be prevented? 

 

Selected Publications

Darcq E, Ben Hamida S, Wu S, Phamluong K, Kharazia V, Xu J, Lombroso P, Ron D.  Inhibition of striatal-enriched tyrosine phosphatase 61 in the dorsomedial striatum is required for the development of excessive ethanol consumption.  J Neurochem. 3 MAR 2014.  DOI: 10.1111/jnc.12701. [Epub ahead of print].

Ben Hamida S, Darcq E, Wang J, Wu S, Phamluong K, Kharazia V, Ron D.  The tyrosine PTPalpha in the dorsomedial striatum promotes excessive ethanol drinking behaviors.  J Neurosci 4;33(36):14369-78, 2013.

Seif T, Chang S-J, Simms JA, Gibb SL, Dadgar J, Chen BT, Harvey BK, Ron D, Messing RO, Bonci A, Hopf FW.  Cortical activation of accumbens hyperpolarization-active NMDARs mediates aversion-resistant alcohol intake. Nature Neurosci 16(8):1094-1100, 2013.

Barak S, Liu F, Ben Hamida S, Yowell QV, Neasta J, Kharazia V, Janak PH, Ron D.  Disruption of alcohol-related memories by mTORC1 inhibition prevents relapse.  Nature Neurosci 16(8):1111-7, 2013. See also http://www.nature.com/news/blocking-boozy-memories-reduces-risk-of-relapse-1.13252.

Ahmadiantehrani S and Ron D.  Dopamine D2 receptor activation leads to the up-regulation of GDNF via Gβγ-Erk1/2-dependent induction of Zif268. J Neurochem 125:193-204, 2013.

Waurnalt V, Darcq E, Levine A, Barak S, Ron D.  Chromatin remodeling – A novel strategy to control excessive alcohol drinking. Translational Psychiatry (Nature Press) 3:e231, 2013.

Ben Hamida S, Neasta J, Lasek AW, Kharazia V, Zou M, Carnicella S, Janak PH, Ron D.  The small G protein H-Ras in the mesolimbic system is a molecular gateway to alcohol-seeking and excessive drinking behaviors.  J Neurosci 32:15849-15858, 2012.

Wang J, Ben Hamida S, Darcq E, Zhu W, Gibb, SL, Lanfranco MF, Carnicella S, Ron D.  Ethanol-mediated facilitation of AMPA Receptor Function in the Dorsomedial Striatum:  Implication for Alcohol Drinking Behavior.  J Neurosci 32:15124-15132, 2012.

Barak S, Ahmadiantehrani S, Kharazia V, Ron D.  Positive autoregulatory feedback loop of GDNF in the ventral tegmental area: implications for alcohol abuse disorders.  Translational Psychiatry (Nature Press) 1:doi:10.1038/tp.2011.57, 2011.

Neasta J, Kiely PA, He D-Y, Adams DR, O’Connor R, Ron D.  Direct interaction between the scaffolding proteins RACK1 and 14-3-3ζ regulates BDNF transcription.  J Biol Chem 287:322-336, 2012.

Gibb SL, Ben Hamida S, Lanfranco MF, Ron D. Ethanol-induced increase in Fyn kinase activity in the dorsomedial striatum is associated with subcellular redistribution of PTPa.  J Neurochem 119:879-889, 2011.

Neasta J, Ben Hamida S, Yowell QV, Carnicella S, Ron D.  AKT signaling pathway in the nucleus accumbens mediates excessive alcohol drinking behaviors.  Biological Psychiatry 70:575-582, 2011.

Barak S, Yowell QV, Carnicella S, Ron D.  Glial cell line-derived neurotrophic factor reverses alcohol-induced allostasis of the mesolimbic dopaminergic system: implications for alcohol reward and seeking.  J Neurosci 31:9885-9894, 2011.

Nie H, Rewal M, Gill TM, Ron D, Janak PH.  Extrasynaptic -containing GABA receptors in the nucleus accumbens dorsomedial shell contribute to alcohol intake.  Proc Natl Acad Sci USA. 108:4459-4464, 2011.

Gibb SL, Jeanblanc J, Barak S, Yowell QV, Yaka R, Ron D.   Lyn kinase regulates mesolimbic dopamine release:  implication for alcohol reward.  J Neurosci 31:2180-2187, 2011.

Neasta J, Ben Hamida S, Yowell Q, Carnicella S, Ron D.  A role for mTOR complex 1 signaling in neuroadaptations underlying alcohol-related disorders.  Proc Natl Acad Sci USA 107:20093-20098, 2010.

Wang J, Carnicella S, He D-Y, Ahmadiantehrani S, Barak S, Ben Hamida S, Kharazia V, Zapata A, Shippenberg TS, Ron D.  Nucleus accumbens-derived GDNF is a retrograde enhancer of dopaminergic tone in the mesocorticolimbic system.  J Neurosci 30:14502-14512, 2010.

Wang J, Lanfranco MF, Gibb SL, Yowell QV, Carnicella S, Ron D.  Long-lasting adaptations of the NR2B-containing NMDA receptors in the dorsomedial striatum play a crucial role in alcohol consumption and relapse.  J Neurosci 30:10187-10198, 2010.

He D-Y, Neasta J, Ron D.  Epigenetic regulation of BDNF expression via the scaffolding protein RACK1.  J Biol Chem 285:19043-19050, 2010.

Jeanblanc J, He D-Y, Logrip ML, Carnicella S, Kharazia V, Janak PH, Ron D.  Endogenous BDNF in the dorsolateral striatum gates alcohol drinking.  J Neurosci 29:13494-13502, 2009.

Carnicella S, Ahmadiantherani S, He D-Y, Nielsen CK, Bartlett SE, Janak PH, Ron D.  Cabergoline decreases alcohol drinking and seeking behaviors via GDNF.  Biological Psychiatry 66:146-153, 2009.