Chronic Carbamazepine Decreases the Incorporation Rate and Turnover of Arachidonic Acid but Not Docosahexaenoic Acid in Brain Phospholipids of the Unanesthetized Rat: Relevance to Bipolar Disorder

Bazinet, Richard P.; Rao, Jagadeesh S.; Chang, Lisa; Rapoport, Stanley I.; Lee, Ho‐Joo

doi:10.1016/j.biopsych.2005.07.024

Cited by 93 publications

(83 citation statements)

References 62 publications

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“…CBZ-treated rats received 25 mg/kg intraperitoneally once daily for 30 days (Sigma-Aldrich). The CBZ was dissolved in a 50:50 (v/v) dimethyl sulfoxide (DMSO, ≥99.9% Sigma-Aldrich): saline (0.9% NaCl, Hospira Inc., Lake Forest, IL, USA) mixture and kept at 37°C as described previously [2,11,27]. A control group received the same volume of DMSO:saline (vehicle) under parallel conditions.…”

Section: Drugsmentioning

confidence: 99%

“…Radioactivity was determined at an efficiency of 88% in 100 μl of the lower organic phase by liquid scintillation counting. As reported, following 5 min [1-14 C]AA infusion, 98% of total plasma radioactivity was radiolabeled AA [11]. Concentrations of unesterified fatty acids were determined in 100-150 μl of the frozen arterial plasma.…”

Section: Chemical Analysismentioning

confidence: 99%

“…Unesterified fatty acids were scraped from the plate and methylated with 1% H 2 SO 4 in anhydrous methanol for 3 h at 70°C. Fatty acid methyl esters were then separated and quantified by gas chromatography using an internal standard, heptadecanoic acid (17:0) [11].…”

Section: Chemical Analysismentioning

confidence: 99%

“…The signaling process can be imaged in unanesthetized rats by injecting intravenously [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]AA and measuring tracer AA uptake into brain using quantitative autoradiography. Regional brain AA incorporation coefficients k* (brain radioactivity/integrated plasma radioactivity) are calculated and, if multiplied by unlabeled unesterified plasma AA concentrations, are converted to regional incorporation rates J in that represent regional brain AA consumption.…”

Section: Introductionmentioning

confidence: 99%

“…vehicle or CBZ 25 mg/kg, then administered saline (control) or quinpirole (1.0 mg/kg i.v.). The CBZ regimen produces a plasma CBZ concentration of 54 μM, at the high end found in CBZ-treated bipolar patients (51 μM), and decreases AA turnover in brain phospholipids and the brain PGE 2 concentration [2,11,18,27]. The quinpirole dose increases k* for AA significantly in brain dopaminergic circuits [5,15].…”

Section: Introductionmentioning

confidence: 99%

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Chronic Carbamazepine Administration Attenuates Dopamine D2-like Receptor-Initiated Signaling via Arachidonic Acid in Rat Brain

et al. 2008

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Observations that dopaminergic antagonists are beneficial in bipolar disorder and that dopaminergic agonists can produce mania suggest that bipolar disorder involves excessive dopaminergic transmission. Thus, mood stabilizers used to treat the disease might act in part by downregulating dopaminergic transmission. In agreement, we reported that dopamine D 2 -like receptor mediated signaling involving arachidonic acid (AA, 20:4n-6) was downregulated in rats chronically treated with lithium. To see whether chronic carbamazepine, another mood stabilizer, did this as well, we injected i.p. saline or the D 2 -like receptor agonist, quinpirole (1 mg/kg), into unanesthetized rats that had been pretreated for 30 days with i.p. carbamazepine (25 mg/kg/day) or vehicle, and used quantitative autoradiography to measure regional brain incorporation coefficients (k*) for AA, markers of signaling. We also measured brain prostaglandin E 2 (PGE 2 ), an AA metabolite. In vehicle-treated rats, quinpirole compared with saline significantly increased k* for AA in 35 of 82 brain regions examined, as well as brain PGE 2 concentration. Affected regions belong to dopaminergic circuits and have high D 2 -like receptor densities. Chronic carbamazepine pretreatment prevented the quinpirole-induced increments in k* and in PGE 2 . These findings are consistent with the hypothesis that effective mood stabilizers generally downregulate brain AA signaling via D 2 -like receptors, and that this signaling is upregulated in bipolar disorder.

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Section: Drugsmentioning

confidence: 99%

Section: Chemical Analysismentioning

confidence: 99%

Section: Chemical Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chronic Carbamazepine Administration Attenuates Dopamine D2-like Receptor-Initiated Signaling via Arachidonic Acid in Rat Brain

et al. 2008

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Lipids in the Treatment of Mental Disorders

Lange

2020

Bailey's Industrial Oil and Fat Products

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The management of mental disorders is dominated today by pharmacotherapy, while nutrition and dietary approaches play a minor role. Evidence from both preclinical and clinical investigations suggests an important role for lipids in major mental disorders. Alterations in the concentration, organization, and metabolism of lipids are associated with mood disorders, schizophrenia, and behavioral problems in childhood. The lipid composition of the brain can be influenced by nutrition, environmental factors, and behavioral activity. Lipids, and omega‐3 polyunsaturated fatty acids (PUFAs) in particular, may represent a target for the prevention and treatment of mental disorders. Deficits in the dietary omega‐3 PUFAs, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been implicated in the pathophysiology of several mental disorders and linked to the maintenance of brain health. This may be mediated by the modulation of inflammatory processes and direct effects on neuronal membrane fluidity and receptor function. Low levels of omega‐3 PUFAs have been associated with various mental disorders, such as poor cognition, depression, anxiety disorders, schizophrenia, and attention‐deficit/hyperactivity disorder (ADHD). The available findings from randomized clinical trials examining the therapeutic efficacy of omega‐3 PUFAs are inconsistent and inconclusive. This limits their usage in psychiatric practice. Future research should investigate the molecular mechanisms underlying the effects of omega‐3 PUFAs in mental disorders. Large‐scale, well‐designed clinical trials should be conducted to assess the efficacy of omega‐3 PUFAs in the prevention and therapy of various mental disorders.

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DHA Esterified to Phosphatidylserine or Phosphatidylcholine is More Efficient at Targeting the Brain than DHA Esterified to Triacylglycerol

Chouinard‐Watkins

Lacombe

Metherel

et al. 2019

Molecular Nutrition Food Res

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Scope: Docosahexaenoic acid (DHA, 22:6n-3) is crucial for optimal neuronal development and function, but the brain has a poor capacity to synthesize this fatty acid. When consumed acutely esterified to phosphatidylcholine, DHA is more efficient at targeting the brain than when consumed esterified to triacylglycerol. However, the brain DHA bioavailability of other forms of DHA-containing phospholipids, after oral ingestion, is unknown. The objective of this study is to compare brain uptake of DHA after acute gavage with different DHA carriers. Methods and results: Ten-week-old rats were gavaged with 3 H-labeled DHA esterified to phosphatidylcholine (DHA-PtdCho), phosphatidylethanolamine (DHA-PtdEtn), phosphatidylserine (DHA-PtdSer) or triacylglycerol (DHA-TG). Six hours post-gavage, the animals were euthanized and radioactivity was quantified in the cortex and serum lipid classes. Radioactivity recovered in cortex total phospholipids was similar between the DHA-PtdCho and DHA-PtdSer groups and were 5.8 and 6.7 times higher than in the DHA-TG group, respectively. Serum total lipid radioactivity was higher in the DHA-PtdSer group than in the DHA-PtdCho and DHA-PtdEtn groups, but not compared to the DHA-TG group. Conclusion: These results suggest that different mechanisms must be present to explain the serum and brain bioavailability differences between DHA-PtdCho and DHA-PtdSer, but these require further investigation.

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Chronic Carbamazepine Decreases the Incorporation Rate and Turnover of Arachidonic Acid but Not Docosahexaenoic Acid in Brain Phospholipids of the Unanesthetized Rat: Relevance to Bipolar Disorder

Cited by 93 publications

References 62 publications

Chronic Carbamazepine Administration Attenuates Dopamine D2-like Receptor-Initiated Signaling via Arachidonic Acid in Rat Brain

Chronic Carbamazepine Administration Attenuates Dopamine D2-like Receptor-Initiated Signaling via Arachidonic Acid in Rat Brain

Lipids in the Treatment of Mental Disorders

DHA Esterified to Phosphatidylserine or Phosphatidylcholine is More Efficient at Targeting the Brain than DHA Esterified to Triacylglycerol

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