ArticlePsychopharmacology2005
Chronic valproate does not alter the kinetics of docosahexaenoic acid within brain phospholipids of the unanesthetized rat.
Article in Psychopharmacology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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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Who cites it
28 citing papers in PubMed, 53 citations in OpenAlex.
- Compound-Specific Isotope Analysis as a Potential Approach for Investigation of Cerebral Accumulation of Docosahexaenoic Acid: Previous Milestones and Recent Trends.Molecular neurobiology · 2025Review
- Lipid metabolism, remodelling and intercellular transfer in the CNS.Nature reviews. Neuroscience · 2025Review
- Turnover of brain DHA in mice is accurately determined by tracer-free natural abundance carbon isotope ratio analysis.Journal of lipid research · 2020Article
- Valnoctamide, which reduces rat brain arachidonic acid turnover, is a potential non-teratogenic valproate substitute to treat bipolar disorder.Psychiatry research · 2017Article
- Abnormal fatty acid pattern in the superior temporal gyrus distinguishes bipolar disorder from major depression and schizophrenia and resembles multiple sclerosis.Psychiatry research · 2014Article
- Propylisopropylacetic acid (PIA), a constitutional isomer of valproic acid, uncompetitively inhibits arachidonic acid acylation by rat acyl-CoA synthetase 4: a potential drug for bipolar disorder.Biochimica et biophysica acta · 2013Article
- Chronic clozapine reduces rat brain arachidonic acid metabolism by reducing plasma arachidonic acid availability.Journal of neurochemistry · 2013Article
- Effects of chronic clozapine administration on markers of arachidonic acid cascade and synaptic integrity in rat brain.Psychopharmacology · 2012Article
- Transcriptional repression of the α7 nicotinic acetylcholine receptor subunit gene (CHRNA7) by activating protein-2α (AP-2α).The Journal of biological chemistry · 2011Article
- Chronic valproate treatment blocks D2-like receptor-mediated brain signaling via arachidonic acid in rats.Neuropharmacology · 2011Article
- Valproate uncompetitively inhibits arachidonic acid acylation by rat acyl-CoA synthetase 4: relevance to valproate's efficacy against bipolar disorder.Biochimica et biophysica acta · 2011Article
- Imaging decreased brain docosahexaenoic acid metabolism and signaling in iPLA(2)β (VIA)-deficient mice.Journal of lipid research · 2010Article
- Extracellular-derived calcium does not initiate in vivo neurotransmission involving docosahexaenoic acid.Journal of lipid research · 2010Article
- Chronic imipramine but not bupropion increases arachidonic acid signaling in rat brain: is this related to 'switching' in bipolar disorder?Molecular psychiatry · 2010Article
- Bipolar disorder and mechanisms of action of mood stabilizers.Brain research reviews · 2009Review
- Mood-stabilizers target the brain arachidonic acid cascade.Current molecular pharmacology · 2009Review
- Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?Molecular psychiatry · 2008Review
- Neuronal peroxisome proliferator-activated receptor gamma signaling: regulation by mood-stabilizer valproate.Journal of molecular neuroscience : MN · 2008Article
- Up-regulation of cPLA(2) gene expression in astrocytes by all three conventional anti-bipolar drugs is drug-specific and enzyme-specific.Psychopharmacology · 2007Article
- Chronic lamotrigine does not alter the turnover of arachidonic acid within brain phospholipids of the unanesthetized rat: implications for the treatment of bipolar disorder.Psychopharmacology · 2007Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleIt has been reported that each of three drugs effective in treating bipolar disorder (lithium, carbamazepine, and valproate) decreases the turnover of arachidonic acid (AA, 20:4n-6) in brain phospholipids of the awake rat. It is also known that lithium and carbamazepine do so without decreasing the turnover of docosahexaenoic acid (DHA, 22:6n-3).
objectiveThe aim of this study was to see whether valproate also specifically targets the turnover of AA but not of DHA in brain phospholipids.
methodsValproate was administered (200 mg kg(-1), i.p.) to rats for 30 days to produce a therapeutically relevant plasma concentration and then determine its effect compared with that of vehicle on incorporation and turnover rates of DHA in brain phospholipids. In unanesthetized rats that had received valproate or vehicle, [1-14C]DHA was infused intravenously, and arterial blood plasma was sampled until the animal was killed at 5 min; and its brain, after being microwaved, was subjected to chemical and radiotracer analysis.
resultsUsing equations derived from our fatty acid model, it was found that chronic valproate compared with vehicle did not alter the rate of incorporation or turnover of DHA in brain phospholipids. Valproate-treated animals had higher concentrations of linoleic acid (18:2n-6) in several brain phospholipids, supporting the hypothesis that it alters brain n-6 fatty acid metabolism.
conclusionsThe results, comparable to published findings following chronic administration of lithium and carbamazepine to rats, support the hypothesis that drugs are effective against mania in bipolar disorder act by downregulating incorporation and turnover of AA, but not of DHA, in brain phospholipids.
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