ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2009
Imaging elevated brain arachidonic acid signaling in unanesthetized serotonin transporter (5-HTT)-deficient mice.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- Sex Differences in Dietary-Induced Liver Steatosis and Insulin Receptor-Related Signaling in Aged Mice Lacking Serotonin Transporter.International journal of molecular sciences · 2026Article
- Radiosynthesis of 20-[Prostaglandins, leukotrienes, and essential fatty acids · 2022Article
- Tissue pretreatment for LC-MS/MS analysis of PUFA and eicosanoid distribution in mouse brain and liver.Analytical and bioanalytical chemistry · 2020Article
- Brain serotonin transporter binding, plasma arachidonic acid and depression severity: A positron emission tomography study of major depression.Journal of affective disorders · 2019Article
- Alterations of Expression of the Serotonin 5-HT4 Receptor in Brain Disorders.International journal of molecular sciences · 2018Review
- Receptor binding profiles and behavioral pharmacology of ring-substituted N,N-diallyltryptamine analogs.Neuropharmacology · 2018Article
- Eag1 KOxidative medicine and cellular longevity · 2017Review
- Transient postnatal fluoxetine decreases brain concentrations of 20-HETE and 15-epi-LXA4, arachidonic acid metabolites in adult mice.Prostaglandins, leukotrienes, and essential fatty acids · 2015Article
- Transient postnatal fluoxetine leads to decreased brain arachidonic acid metabolism and cytochrome P450 4A in adult mice.Prostaglandins, leukotrienes, and essential fatty acids · 2014Article
- An evaluation of the serotonin system and perseverative, compulsive, stereotypical, and hyperactive behaviors in dopamine transporter (DAT) knockout mice.Psychopharmacology · 2013Article
- Genetic and pharmacological manipulations of the serotonergic system in early life: neurodevelopmental underpinnings of autism-related behavior.Frontiers in cellular neuroscience · 2013Article
- Chronic treatment with anti-bipolar drugs causes intracellular alkalinization in astrocytes, altering their functions.Neurochemical research · 2012Review
- The synthesis and in vivo pharmacokinetics of fluorinated arachidonic acid: implications for imaging neuroinflammation.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2012Article
- Lamotrigine blocks NMDA receptor-initiated arachidonic acid signalling in rat brain: implications for its efficacy in bipolar disorder.The international journal of neuropsychopharmacology · 2012Article
- Knocking out the dopamine reuptake transporter (DAT) does not change the baseline brain arachidonic acid signal in the mouse.The International journal of neuroscience · 2012Article
- Imaging brain signal transduction and metabolism via arachidonic and docosahexaenoic acid in animals and humans.Brain research bulletin · 2012Review
- Altered 5-HT2C receptor agonist-induced responses and 5-HT2C receptor RNA editing in the amygdala of serotonin transporter knockout mice.BMC pharmacology · 2011Article
- Disturbed neurotransmitter transporter expression in Alzheimer's disease brain.Journal of Alzheimer's disease : JAD · 2011Article
- The serotonin 5-HT(2A) receptor agonist TCB-2: a behavioral and neurophysiological analysis.Psychopharmacology · 2010Article
- Functional interactions between 5-HT2A and presynaptic 5-HT1A receptor-based responses in mice genetically deficient in the serotonin 5-HT transporter (SERT).British journal of pharmacology · 2010Article
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8 authors at 3 institutions in 1 country.
Funding
Abstract
Certain polymorphisms reduce serotonin (5-HT) reuptake transporter (5-HTT) function and increase susceptibility to psychiatric disorders. Heterozygous (5-HTT(+/-))-deficient mice, models for humans with these polymorphisms, have elevated brain 5-HT concentrations and behavioral abnormalities. As postsynaptic 5-HT(2A/2C) receptors are coupled to cytosolic phospholipase A(2) (cPLA(2)), which releases arachidonic acid (AA) from membrane phospholipid, 5-HTT-deficient mice may have altered brain AA signaling and metabolism. To test this hypothesis, signaling was imaged as an AA incorporation coefficient k(*) in unanesthetized homozygous knockout (5-HTT(-/-)), 5-HTT(+/-) and wild-type (5-HTT(+/+)), mice following saline (baseline) or 1.5 mg/kg s.c. DOI, a partial 5-HT(2A/2C) receptor agonist. Enzyme activities, metabolite concentrations, and head-twitch responses to DOI were also measured. Baseline k(*) was widely elevated by 20-70% in brains of 5-HTT(+/-) and 5-HTT(-/-) compared to 5-HTT(+/+) mice. DOI increased k(*) in 5-HTT(+/+) mice, but decreased k(*) in 5-HTT-deficient mice. Brain cPLA(2) activity was elevated in 5-HTT-deficient mice; cyclooxygenase activity and prostaglandin E(2) and F(2alpha) and thromboxane B(2) concentrations were reduced. Head-twitch responses to DOI, although robust in 5-HTT(+/+) and 5-HTT(+/-) mice, were markedly fewer in 5-HTT(-/-) mice. Pretreatment with para-chlorophenylalanine, a 5-HT synthesis inhibitor, restored head twitches in 5-HTT(-/-) mice to levels in 5-HTT(+/+) mice. We propose that increased baseline values of k(*) in 5-HTT-deficient mice reflect tonic cPLA(2) stimulation through 5-HT(2A/2C) receptors occupied by excess 5-HT, and that reduced k(*) and head-twitch responses to DOI reflected displacement of receptor-bound 5-HT by DOI with a lower affinity. Increased baseline AA signaling in humans having polymorphisms with reduced 5-HTT function might be identified using positron emission tomography.
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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.