ArticleBiological psychiatry2009
Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) controls activation of extracellular signal-regulated kinase (ERK) signaling in the striatum and long-term behavioral responses to cocaine.
Article in Biological psychiatry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- The Signaling and Pharmacology of the Dopamine D1 Receptor.Frontiers in cellular neuroscience · 2021Pooled it
- Cocaine-Induced Immediate-Early Gene Expression in the Nucleus Accumbens: Roles of Separate cAMP Sensors.Journal of neurochemistry · 2026Article
- PKD1-mediated phosphorylation at dopamine D2 receptor serine 365 site in dorsal striatum underlies cocaine-induced locomotor hyperactivity.IBRO neuroscience reports · 2025Article
- Individual NMDA receptor GluN2 subunit signaling domains differentially regulate the postnatal maturation of hippocampal excitatory synaptic transmission and plasticity but not dendritic morphology.Synapse (New York, N.Y.) · 2024Article
- Gynecological surgery in adulthood imparts cognitive and brain changes in rats: A focus on hysterectomy at short-, moderate-, and long-term intervals after surgery.Hormones and behavior · 2023Article
- Article
- Researching Mitigation of Alcohol Binge Drinking in Polydrug Abuse: KCNK13 and RASGRF2 Gene(s) Risk Polymorphisms Coupled with Genetic Addiction Risk Severity (GARS) Guiding Precision Pro-Dopamine Regulation.Journal of personalized medicine · 2022Article
- Segregation of D1 and D2 dopamine receptors in the striatal direct and indirect pathways: An historical perspective.Frontiers in synaptic neuroscience · 2022Review
- Nicotine self-administration and ERK signaling are altered in RasGRF2 knockout mice.Frontiers in pharmacology · 2022Article
- A Rational Design of α-Helix-Shaped Peptides Employing the Hydrogen-Bond Surrogate Approach: A Modulation Strategy for Ras-RasGRF1 Interaction in Neuropsychiatric Disorders.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Cocaine-Dependent Acquisition of Locomotor Sensitization and Conditioned Place Preference Requires D1 Dopaminergic Signaling through a Cyclic AMP, NCS-Rapgef2, ERK, and Egr-1/Zif268 Pathway.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Ras GEF Mouse Models for the Analysis of Ras Biology and Signaling.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Dopamine D1 and Glutamate Receptors Co-operate With Brain-Derived Neurotrophic Factor (BDNF) and TrkB to Modulate ERK Signaling in Adult Striatal Slices.Frontiers in cellular neuroscience · 2020Article
- The Inhibition of RasGRF2, But Not RasGRF1, Alters Cocaine Reward in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Genetic enhancement of Ras-ERK pathway does not aggravate L-DOPA-induced dyskinesia in mice but prevents the decrease induced by lovastatin.Scientific reports · 2018Article
- Human Endogenous Retrovirus-K HML-2 integration withinProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Article
- ΔCannabis and cannabinoid research · 2017Article
- Ifenprodil Attenuates Methamphetamine-Induced Behavioral Sensitization and Activation of Ras-ERK-∆FosB Pathway in the Caudate Putamen.Neurochemical research · 2016Article
- Impairment of cocaine-mediated behaviours in mice by clinically relevant Ras-ERK inhibitors.eLife · 2016Article
Corrections and comments
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Authors and funding
13 authors at 9 institutions in 5 countries.
Funding
Abstract
backgroundRas-extracellular signal-regulated kinase (Ras-ERK) signaling is central to the molecular machinery underlying cognitive functions. In the striatum, ERK1/2 kinases are co-activated by glutamate and dopamine D1/5 receptors, but the mechanisms providing such signaling integration are still unknown. The Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1), a neuronal specific activator of Ras-ERK signaling, is a likely candidate for coupling these neurotransmitter signals to ERK kinases in the striatonigral medium spiny neurons (MSN) and for modulating behavioral responses to drug abuse such as cocaine.
methodsWe used genetically modified mouse mutants for Ras-GRF1 as a source of primary MSN cultures and organotypic slices, to perform both immunoblot and immunofluorescence studies in response to glutamate and dopamine receptor agonists. Mice were also subjected to behavioral and immunohistochemical investigations upon treatment with cocaine.
resultsPhosphorylation of ERK1/2 in response to glutamate, dopamine D1 agonist, or both stimuli simultaneously is impaired in Ras-GRF1-deficient striatal cells and organotypic slices of the striatonigral MSN compartment. Consistently, behavioral responses to cocaine are also affected in mice deficient for Ras-GRF1 or overexpressing it. Both locomotor sensitization and conditioned place preference are significantly attenuated in Ras-GRF1-deficient mice, whereas a robust facilitation is observed in overexpressing transgenic animals. Finally, we found corresponding changes in ERK1/2 activation and in accumulation of FosB/DeltaFosB, a well-characterized marker for long-term responses to cocaine, in MSN from these animals.
conclusionsThese results strongly implicate Ras-GRF1 in the integration of the two main neurotransmitter inputs to the striatum and in the maladaptive modulation of striatal networks in response to cocaine.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.