Abstract | BACKGROUND AND OBJECTIVE: Hyperdopaminergic signaling and an upregulated brain arachidonic acid (AA) cascade may contribute to bipolar disorder (BD). Lithium and carbamazepine, FDA-approved for the treatment of BD, attenuate brain dopaminergic D(2)-like (D(2), D(3), and D(4)) receptor signaling involving AA when given chronically to awake rats. We hypothesized that valproate (VPA), with mood-stabilizing properties, would also reduce D(2)-like-mediated signaling via AA. METHODS: An acute dose of quinpirole (1 mg/kg) or saline was administered to unanesthetized rats that had been treated for 30 days with a therapeutically relevant dose of VPA (200 mg/kg/day) or vehicle. Regional brain AA incorporation coefficients, k*, and incorporation rates, J(in), markers of AA signaling and metabolism, were measured by quantitative autoradiography after intravenous [1-(14)C]AA infusion. Whole brain concentrations of prostaglandin (PG)E(2) and thromboxane (TX) B(2) also were measured. RESULTS:
Quinpirole compared to saline significantly increased k* in 40 of 83 brain regions, and increased brain concentrations of PGE(2) in chronic vehicle-treated rats. VPA treatment by itself reduced concentrations of plasma unesterified AA and whole brain PGE(2) and TXB(2), and blocked the quinpirole-induced increments in k* and PGE(2). CONCLUSION: These results further provide evidence that mood stabilizers downregulate brain dopaminergic D(2)-like receptor signaling involving AA.
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Authors | Epolia Ramadan, Mireille Basselin, Ameer Y Taha, Yewon Cheon, Lisa Chang, Mei Chen, Stanley I Rapoport |
Journal | Neuropharmacology
(Neuropharmacology)
Vol. 61
Issue 8
Pg. 1256-64
(Dec 2011)
ISSN: 1873-7064 [Electronic] England |
PMID | 21839100
(Publication Type: Journal Article, Research Support, N.I.H., Intramural)
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Copyright | Published by Elsevier Ltd. |
Chemical References |
- Antimanic Agents
- Carbon Radioisotopes
- Dopamine Agonists
- Dopamine Antagonists
- Receptors, Dopamine D2
- Arachidonic Acid
- Thromboxane B2
- Valproic Acid
- Dinoprostone
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Topics |
- Analysis of Variance
- Animals
- Antimanic Agents
(blood, pharmacology)
- Arachidonic Acid
(metabolism, pharmacokinetics)
- Autoradiography
- Brain
(drug effects, metabolism)
- Carbon Radioisotopes
(pharmacokinetics)
- Dinoprostone
(metabolism)
- Dopamine Agonists
(pharmacology)
- Dopamine Antagonists
(pharmacology)
- Male
- Rats
- Rats, Inbred F344
- Receptors, Dopamine D2
(metabolism)
- Signal Transduction
(drug effects)
- Thromboxane B2
(metabolism)
- Valproic Acid
(blood, pharmacology)
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