ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2021
cAMP-Fyn signaling in the dorsomedial striatum direct pathway drives excessive alcohol use.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Neutrophil extracellular traps (NETs) and NETosis in alcohol-associated diseases: A systematic review.Alcohol, clinical & experimental research · 2025Pooled it
- PDE4 inhibitor rolipram dynamically regulates the balance between D1-MSNs and D2-MSNs in the DMS to modulate abnormal "Go" behavior associated with alcohol addiction.Acta pharmacologica Sinica · 2026Article
- Early life adversity increases striatal dopamine D1 receptor density and promotes social alcohol drinking in mice, especially males.Translational psychiatry · 2026Article
- Prosapip1 (encoded by theeLife · 2025Article
- Early life adversity increases striatal dopamine D1 receptor density and promotes social alcohol drinking in mice, especially males.bioRxiv : the preprint server for biology · 2025Article
- Alcohol effects on associative and sensorimotor cortico-thalamo-basal ganglia circuits alter decision making and alcohol intake.Alcohol (Fayetteville, N.Y.) · 2025Review
- Preexisting risk-avoidance and enhanced alcohol relief are driven by imbalance of the striatal dopamine receptors in mice.Nature communications · 2024Article
- Leucine-rich repeat kinase 2 limits dopamine D1 receptor signaling in striatum and biases against heavy persistent alcohol drinking.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
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- Inhibition of Phosphodiesterase 2 Ameliorates Post-Traumatic Stress-Induced Alcohol Intake Disorder by Regulating cAMP/cGMP Signaling.The international journal of neuropsychopharmacology · 2022Article
- Alcohol and the brain: from genes to circuits.Trends in neurosciences · 2021Review
- Saracatinib Fails to Reduce Alcohol-Seeking and Consumption in Mice and Human Participants.Frontiers in psychiatry · 2021Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Fyn kinase in the dorsomedial striatum (DMS) of rodents plays a central role in mechanisms underlying excessive alcohol intake. The DMS is comprised of medium spiny neurons (MSNs) that project directly (dMSNs) or indirectly (iMSNs) to the substantia nigra. Here, we examined the cell-type specificity of Fyn's actions in alcohol use. First, we knocked down Fyn selectively in DMS dMSNs or iMSNs of mice and measured the level of alcohol consumption. We found that downregulation of Fyn in dMSNs, but not in iMSNs, reduces excessive alcohol but not saccharin intake. D1Rs are coupled to Gαs/olf, which activate cAMP signaling. To examine whether Fyn's actions are mediated through cAMP signaling, DMS dMSNs were infected with GαsDREADD, and the activation of Fyn signaling was measured following CNO treatment. We found that remote stimulation of cAMP signaling in DMS dMSNs activates Fyn and promotes the phosphorylation of the Fyn substrate, GluN2B. In contract, remote activation of GαsDREADD in DLS dMSNs did not alter Fyn signaling. We then tested whether activation of GαsDREADD in DMS dMSNs or iMSNs alters alcohol intake and observed that CNO-dependent activation of GαsDREADD in DMS dMSNs but not iMSNs increases alcohol but not saccharin intake. Finally, we examined the contribution of Fyn to GαsDREADD-dependent increase in alcohol intake, and found that systemic administration of the Fyn inhibitor, AZD0503 blocks GαsDREADD-dependent increase in alcohol consumption. Our results suggest that the cAMP-Fyn axis in the DMS dMSNs is a molecular transducer of mechanisms underlying the development of excessive alcohol consumption.
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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.