ArticleMolecular psychiatry2018
The Arf6 activator Efa6/PSD3 confers regional specificity and modulates ethanol consumption in Drosophila and humans.
Article in Molecular psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- The IMAGEN study: a decade of imaging genetics in adolescents.Molecular psychiatry · 2020Pooled it
- Chemical Genetic Screen Identifies PSD3 as a Direct Substrate of NUAK1 that Regulates Dendritic Spine Maturation.bioRxiv : the preprint server for biology · 2026Article
- Abnormal Endocytosis Resulting from Imbalanced Proteomic Doses in Human Aneuploid Embryos.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Bitter Sensing ProtectsThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- From Natural Behavior to Drug Screening: Invertebrates as Models to Study Mechanisms Associated with Alcohol Use Disorders.Current topics in behavioral neurosciences · 2025Review
- Synaptic Mechanisms of Ethanol Tolerance and Neuroplasticity: Insights from Invertebrate Models.International journal of molecular sciences · 2024Review
- Large analysis of genetic manipulations reveals an inverse correlation between initial alcohol resistance and rapid tolerance phenotypes.Genes, brain, and behavior · 2024Article
- Large genetic analysis of alcohol resistance and tolerance reveals an inverse correlation and suggests 'true' tolerance mutants.bioRxiv : the preprint server for biology · 2023Article
- The Stage-Based Model of Addiction-UsingInternational journal of molecular sciences · 2023Review
- Molecular Abnormalities in BTBR Mice and Their Relevance to Schizophrenia and Autism Spectrum Disorders: An Overview of Transcriptomic and Proteomic Studies.Biomedicines · 2023Article
- The Use ofBiomedicines · 2022Review
- Tolerance to alcohol: A critical yet understudied factor in alcohol addiction.Pharmacology, biochemistry, and behavior · 2021Review
- Flying Together:International journal of molecular sciences · 2020Review
- Altered Actin Filament Dynamics in theThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Article
- A Fly's Eye View of Natural and Drug Reward.Frontiers in physiology · 2018Review
- Alcohol-Induced Behaviors Require a Subset of Drosophila JmjC-Domain Histone Demethylases in the Nervous System.Alcoholism, clinical and experimental research · 2017Article
- Review
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Authors and funding
28 authors at 18 institutions in 6 countries.
Funding
Abstract
Ubiquitously expressed genes have been implicated in a variety of specific behaviors, including responses to ethanol. However, the mechanisms that confer this behavioral specificity have remained elusive. Previously, we showed that the ubiquitously expressed small GTPase Arf6 is required for normal ethanol-induced sedation in adult Drosophila. Here, we show that this behavioral response also requires Efa6, one of (at least) three Drosophila Arf6 guanine exchange factors. Ethanol-naive Arf6 and Efa6 mutants were sensitive to ethanol-induced sedation and lacked rapid tolerance upon re-exposure to ethanol, when compared with wild-type flies. In contrast to wild-type flies, both Arf6 and Efa6 mutants preferred alcohol-containing food without prior ethanol experience. An analysis of the human ortholog of Arf6 and orthologs of Efa6 (PSD1-4) revealed that the minor G allele of single nucleotide polymorphism (SNP) rs13265422 in PSD3, as well as a haplotype containing rs13265422, was associated with an increased frequency of drinking and binge drinking episodes in adolescents. The same haplotype was also associated with increased alcohol dependence in an independent European cohort. Unlike the ubiquitously expressed human Arf6 GTPase, PSD3 localization is restricted to the brain, particularly the prefrontal cortex (PFC). Functional magnetic resonance imaging revealed that the same PSD3 haplotype was also associated with a differential functional magnetic resonance imaging signal in the PFC during a Go/No-Go task, which engages PFC-mediated executive control. Our translational analysis, therefore, suggests that PSD3 confers regional specificity to ubiquitous Arf6 in the PFC to modulate human alcohol-drinking behaviors.
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Registered trials
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.