ArticleMolecular psychiatry2023
Impact of membrane lipid polyunsaturation on dopamine D2 receptor ligand binding and signaling.
Article in Molecular psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 0 citations in OpenAlex.
- Canonical and Non-Canonical Antipsychotics' Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia.International journal of molecular sciences · 2023Pooled it
- A Membrane-Centric Plasma Lipidomic Signature of Response to Long-Acting Naltrexone in Alcohol Use Disorder.Addiction biology · 2026Trial
- Membrane lipid poly-unsaturation selectively affects dopamine D2 receptor endocytosis.Nature communications · 2026Article
- Molecular Mechanisms of Menstrual Cycle-Related Suicide Risk: A Selective Review of Promising Candidate Systems.Biological psychiatry · 2026Review
- Progress on Omega-3 fatty acids for the comprehensive and targeted treatment of spinal cord injury.Bone research · 2026Review
- Acute docosahexaenoic acid administration reduces binge-like ethanol consumption and palatable substances in C57BL/6J mice.Frontiers in pharmacology · 2026Article
- The effects of omega-3 fatty acids on Wnt activity in iPSC-derived neural stem cells from adult ADHD patients.Neuroscience applied · 2026Article
- Perinatal omega-3 sex-selectively mitigates neuropsychiatric impacts of prenatal THC in the cortico-striatal-hippocampal circuit.Molecular psychiatry · 2025Article
- Metabolomic Insights into Attention Deficit Hyperactivity Disorder: A Scoping Review.Metabolites · 2025Review
- Prenatal Poly I:C exposure affects tryptophan-kynurenine metabolism associated with intestinal microbiome in female juvenile rats.Frontiers in immunology · 2025Article
- G Protein-Coupled Receptor Dimerization-What Next?International journal of molecular sciences · 2024Review
- Impact of dietary changes on retinal neuronal plasticity in rodent models of physical and psychological trauma.Frontiers in genetics · 2024Article
- How Neuromembrane Lipids Modulate Membrane Proteins: Insights from G-Protein-Coupled Receptors (GPCRs) and Receptor Tyrosine Kinases (RTKs).Cold Spring Harbor perspectives in biology · 2023Review
- Beyond Fluidity: The Role of Lipid Unsaturation in Membrane Function.Cold Spring Harbor perspectives in biology · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
22 authors at 6 institutions in 4 countries.
Funding
Abstract
Increasing evidence supports a relationship between lipid metabolism and mental health. In particular, the biostatus of polyunsaturated fatty acids (PUFAs) correlates with some symptoms of psychiatric disorders, as well as the efficacy of pharmacological treatments. Recent findings highlight a direct association between brain PUFA levels and dopamine transmission, a major neuromodulatory system implicated in the etiology of psychiatric symptoms. However, the mechanisms underlying this relationship are still unknown. Here we demonstrate that membrane enrichment in the n-3 PUFA docosahexaenoic acid (DHA), potentiates ligand binding to the dopamine D2 receptor (D2R), suggesting that DHA acts as an allosteric modulator of this receptor. Molecular dynamics simulations confirm that DHA has a high preference for interaction with the D2R and show that membrane unsaturation selectively enhances the conformational dynamics of the receptor around its second intracellular loop. We find that membrane unsaturation spares G protein activity but potentiates the recruitment of β-arrestin in cells. Furthermore, in vivo n-3 PUFA deficiency blunts the behavioral effects of two D2R ligands, quinpirole and aripiprazole. These results highlight the importance of membrane unsaturation for D2R activity and provide a putative mechanism for the ability of PUFAs to enhance antipsychotic efficacy.
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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.