Dorit Ron, PhD

Professor

Neurology

[email protected]

415-502-7620

Signal Transduction, Molecular Neurobiology of Addiction

We use molecular biology, biochemistry and electrophysiology, in parallel with behavioral models, to study how normal signaling processes are altered upon exposure of rodents to alcohol and drugs of abuse, and how these changes lead to the development, maintenance or the prevention of addiction.

Current Projects

Identifying the function of the growth factors BDNF, GDNF and IGF1 in the CNS and in alcohol abuse disorders.
Determining the role of the mTor in aberrant synaptic plasticity induced by drugs of abuse.
Identifying the role of tyrosine kinases and phosphatases in alcohol abuse disorders.
Determining the role of the NMDA receptor in alcohol-mediated plasticity in the dorsal striatum.
Exploring the role of scaffolding proteins in the CNS and in alcohol abuse disorders.
Epigenetic mechanisms and addiction.
Identifying the role of HSP90 in alcohol abuse disorders.

Lab Members

Nadege Morrisot
Postdoctoral Fellow
[email protected]

Sophie Laguesse
Postdoctoral Fellow
[email protected]

Samuel Sakhai
Postdoctoral Fellow
[email protected]

Anna Fiorenza
Postdoctoral Fellow
[email protected]

Benjamin Dorn
Neuroscience Graduate Student
[email protected]

Khanhky Phamluong
Staff Research Associate
[email protected]

Ji Hwan Yu
Technician
[email protected]

Caitlin Castagnola
Student
[email protected]

Dana Kennedy
Student
[email protected]

Lab Website

Academic community service and committee membership:

PSPG Committee for Student Welfare

Publications:

Paradoxical mTORC1-Dependent microRNA-mediated Translation Repression in the Nucleus Accumbens of Mice Consuming Alcohol Attenuates Glycolysis.

Leucine-rich repeat kinase 2 limits dopamine D1 receptor signaling in striatum and biases against heavy persistent alcohol drinking.

The small G-protein Rac1 in the dorsomedial striatum promotes alcohol-dependent structural plasticity and goal-directed learning in mice.

Alcohol Inhibits Glycolysis in the Nucleus Accumbens of Mice Through mTORC1-Dependent Repression of Translation.

The Small G-Protein Rac1 Promotes Neuroadaptations that Underlie Alcohol Use Disorder.

Identification of Novel BDNF-Specific Corticostriatal Circuitries.

The BDNF Val68Met polymorphism causes a sex specific alcohol preference over social interaction and also acute tolerance to the anxiolytic effects of alcohol, a phenotype driven by malfunction of BDNF in the ventral hippocampus of male mice.

Correction: mTORC1 in the orbitofrontal cortex promotes habitual alcohol seeking.

Alcohol and the brain: from genes to circuits.

Brain-specific inhibition of mTORC1 eliminates side effects resulting from mTORC1 blockade in the periphery and reduces alcohol intake in mice.

A non-hallucinogenic psychedelic analogue with therapeutic potential.

Growth Factors and Alcohol Use Disorder.

Investigating the link between serum concentrations of brain-derived neurotrophic factor and behavioral measures in anxious alcohol-dependent individuals.

Astrocytes and alcohol: cortical astrocytes regulate alcohol consumption and intoxication.

cAMP-Fyn signaling in the dorsomedial striatum direct pathway drives excessive alcohol use.

Differential correlation of serum BDNF and microRNA content in rats with rapid or late onset of heavy alcohol use.

mTORC1 in the orbitofrontal cortex promotes habitual alcohol seeking.

Protein Translation and Psychiatric Disorders.

The Fyn kinase inhibitor, AZD0530, suppresses mouse alcohol self-administration and seeking.

D1 receptor hypersensitivity in mice with low striatal D2 receptors facilitates select cocaine behaviors.

Increasing Brain-Derived Neurotrophic Factor (BDNF) in medial prefrontal cortex selectively reduces excessive drinking in ethanol dependent mice.

Mammalian target of rapamycin complex 1 and its downstream effector collapsin response mediator protein-2 drive reinstatement of alcohol reward seeking.

Special issue on new technologies for alcohol research and treatment.

Mice engineered to mimic a common Val66Met polymorphism in the BDNF gene show greater sensitivity to reversal in environmental contingencies.

GDNF and alcohol use disorder.

Targeting the intracellular signaling "STOP" and "GO" pathways for the treatment of alcohol use disorders.

mTORC2 in the dorsomedial striatum of mice contributes to alcohol-dependent F-Actin polymerization, structural modifications, and consumption.

mTORC1-dependent translation of collapsin response mediator protein-2 drives neuroadaptations underlying excessive alcohol-drinking behaviors.

Prosapip1-Dependent Synaptic Adaptations in the Nucleus Accumbens Drive Alcohol Intake, Seeking, and Reward.

Fyn Signaling Is Compartmentalized to Dopamine D1 Receptor Expressing Neurons in the Dorsal Medial Striatum.

Alcohol operant self-administration: Investigating how alcohol-seeking behaviors predict drinking in mice using two operant approaches.

A new generation of mTORC1 inhibitor attenuates alcohol intake and reward in mice.

Periadolescent Maturation of GABAergic Hyperpolarization at the Axon Initial Segment.

Altered sensitivity to the anxiolytic and rewarding properties of alcohol in mice which carry the BDNF valine 68 to methionine polymorphism.

mTORC1 is a key molecular transducer of alcohol-dependent plasticity, seeking and relapse.

Limited Excessive Voluntary Alcohol Drinking Leads to Liver Dysfunction in Mice.

Alcohol-dependent molecular adaptations of the NMDA receptor system.

Region specific activation of the AKT and mTORC1 pathway in response to excessive alcohol intake in rodents.

The Neurotrophic Factor Receptor p75 in the Rat Dorsolateral Striatum Drives Excessive Alcohol Drinking.

Activation of the cAMP Pathway Induces RACK1-Dependent Binding of ß-Actin to BDNF Promoter.

Molecular mechanisms underlying alcohol-drinking behaviours.

The First Alcohol Drink Triggers mTORC1-Dependent Synaptic Plasticity in Nucleus Accumbens Dopamine D1 Receptor Neurons.

Chapter 13 mTOR and Drugs of Abuse.

Alcohol Elicits Functional and Structural Plasticity Selectively in Dopamine D1 Receptor-Expressing Neurons of the Dorsomedial Striatum.

The BDNF Valine 68 to Methionine Polymorphism Increases Compulsive Alcohol Drinking in Mice That Is Reversed by Tropomyosin Receptor Kinase B Activation.

Striatal-enriched protein tyrosine phosphatase controls responses to aversive stimuli: implication for ethanol drinking.

Corticostriatal BDNF and alcohol addiction.

Glial cell line-derived neurotrophic factor (GDNF) is an endogenous protector in the mesolimbic system against excessive alcohol consumption and relapse.

mTOR complex 1: a key player in neuroadaptations induced by drugs of abuse.

Animal models of excessive alcohol consumption: recent advances and future challenges.

Inhibition of striatal-enriched tyrosine phosphatase 61 in the dorsomedial striatum is sufficient to increased ethanol consumption.

Intermittent ethanol access schedule in rats as a preclinical model of alcohol abuse.

Chapter 9 From Signaling Pathways to Behavior The Light and Dark Sides of Alcohol.

Chromatin remodeling: a new landscape to treat harmful alcohol-use disorders.

Protein tyrosine phosphatase a in the dorsomedial striatum promotes excessive ethanol-drinking behaviors.

RACK1 to the future--a historical perspective.

Cortical activation of accumbens hyperpolarization-active NMDARs mediates aversion-resistant alcohol intake.

Nature Neurosci June 3, 2013 [epub ahead of print]

Disruption of alcohol-related memories by mTORC1 inhibition prevents relapse.

Binge ethanol-drinking potentiates corticotropin releasing factor R1 receptor activity in the ventral tegmental area.

Dopamine D2 receptor activation leads to an up-regulation of glial cell line-derived neurotrophic factor via Gß?-Erk1/2-dependent induction of Zif268.

GDNF is a novel ethanol-responsive gene in the VTA: implications for the development and persistence of excessive drinking.

Addiction Biology January 9, 2013 [epub ahead of print]

Alcohol: Clin Exp Res

J Neurochem

Transl Psychiatry

BDNF-mediated regulation of ethanol consumption requires the activation of the MAP kinase pathway and protein synthesis.

Ethanol-mediated facilitation of AMPA receptor function in the dorsomedial striatum: implications for alcohol drinking behavior.

Recent advances in the discovery and preclinical testing of novel compounds for the prevention and/or treatment of alcohol use disorders.

Addic Biol

Current Topics in Behavioral Neuroscience-Behavioral Neurobiology of Alcohol Addiction

J Biol Chem

J Neurosci

J Neurosci

RACK1, A multifaceted scaffolding protein: Structure and function.

Glial cell line-derived neurotrophic factor reverses alcohol-induced allostasis of the mesolimbic dopaminergic system: implications for alcohol reward and seeking.

Striatal involvement in human alcoholism and alcohol consumption, and withdrawal in animal models.

AKT signaling pathway in the nucleus accumbens mediates excessive alcohol drinking behaviors.

Ethanol-mediated long-lasting adaptations of the NR2B-containing NMDA receptors in the dorsomedial striatum.

Extrasynaptic delta-containing GABAA receptors in the nucleus accumbens dorsomedial shell contribute to alcohol intake.

Lyn kinase regulates mesolimbic dopamine release: implication for alcohol reward.

J Neurochem

J Neurochem

Signaling Pathways Mediating Alcohol Effects.

Role for mammalian target of rapamycin complex 1 signaling in neuroadaptations underlying alcohol-related disorders.

Nucleus accumbens-derived glial cell line-derived neurotrophic factor is a retrograde enhancer of dopaminergic tone in the mesocorticolimbic system.

Regulation of operant oral ethanol self-administration: a dose-response curve study in rats.

Noribogaine, but not 18-MC, exhibits similar actions as ibogaine on GDNF expression and ethanol self-administration.

Long-lasting adaptations of the NR2B-containing NMDA receptors in the dorsomedial striatum play a crucial role in alcohol consumption and relapse.

Epigenetic regulation of BDNF expression via the scaffolding protein RACK1.

Endogenous BDNF in the dorsolateral striatum gates alcohol drinking.

Blockade of ethanol reward by the kappa opioid receptor agonist U50,488H.

Escalating ethanol intake is associated with altered corticostriatal BDNF expression.

GDNF is an endogenous negative regulator of ethanol-mediated reward and of ethanol consumption after a period of abstinence.

Cabergoline decreases alcohol drinking and seeking behaviors via glial cell line-derived neurotrophic factor.

Excessive alcohol consumption is blocked by glial cell line-derived neurotrophic factor.

Alpha4-containing GABAA receptors in the nucleus accumbens mediate moderate intake of alcohol.

GDNF--a potential target to treat addiction.

PKCbetaII modulates translation independently from mTOR and through RACK1.

GDNF is a fast-acting potent inhibitor of alcohol consumption and relapse.

Glial cell line-derived neurotrophic factor reverses ethanol-mediated increases in tyrosine hydroxylase immunoreactivity via altering the activity of heat shock protein 90.

Dynorphin is a downstream effector of striatal BDNF regulation of ethanol intake.

Mind bomb-2 is an E3 ligase that ubiquitinates the N-methyl-D-aspartate receptor NR2B subunit in a phosphorylation-dependent manner.

Protein kinase C and alcohol addiction.

Ethanol induces long-term facilitation of NR2B-NMDA receptor activity in the dorsal striatum: implications for alcohol drinking behavior.

Autoregulation of glial cell line-derived neurotrophic factor expression: implications for the long-lasting actions of the anti-addiction drug, Ibogaine.

Cocaine enhances NMDA receptor-mediated currents in ventral tegmental area cells via dopamine D5 receptor-dependent redistribution of NMDA receptors.

Insulin-like growth factor I controls a mutually exclusive association of RACK1 with protein phosphatase 2A and beta1 integrin to promote cell migration.

Homer isoforms differentially regulate cocaine-induced neuroplasticity.

BIG news in alcohol addiction: new findings on growth factor pathways BDNF, insulin, and GDNF.

From blue states to up states: a regional view of NMDA-ethanol interactions.

The dopamine D3 receptor is part of a homeostatic pathway regulating ethanol consumption.

The "ups and downs" of signaling cascades in addiction.

Ethanol alters trafficking and functional N-methyl-D-aspartate receptor NR2 subunit ratio via H-Ras.

Glial cell line-derived neurotrophic factor mediates the desirable actions of the anti-addiction drug ibogaine against alcohol consumption.

GDNF and addiction.

RACK1 and brain-derived neurotrophic factor: a homeostatic pathway that regulates alcohol addiction.

Signaling cascades regulating NMDA receptor sensitivity to ethanol.

Spatial and temporal regulation of RACK1 function and N-methyl-D-aspartate receptor activity through WD40 motif-mediated dimerization.

Fyn kinase and NR2B-containing NMDA receptors regulate acute ethanol sensitivity but not ethanol intake or conditioned reward.

Cellular adaptation to chronic ethanol results in altered compartmentalization and function of the scaffolding protein RACK1.

Corticotropin-releasing factor requires CRF binding protein to potentiate NMDA receptors via CRF receptor 2 in dopamine neurons.

Scaffolding of Fyn kinase to the NMDA receptor determines brain region sensitivity to ethanol.

H-Ras modulates N-methyl-D-aspartate receptor function via inhibition of Src tyrosine kinase activity.

Pituitary adenylate cyclase-activating polypeptide (PACAP(1-38)) enhances N-methyl-D-aspartate receptor function and brain-derived neurotrophic factor expression via RACK1.

Alcohol addiction.

Glutathione S-transferase pull-down assay.

Ethanol induces gene expression via nuclear compartmentalization of receptor for activated C kinase 1.

NMDA receptor function is regulated by the inhibitory scaffolding protein, RACK1.