scholarly journals Lithium and the Other Mood Stabilizers Effective in Bipolar Disorder Target the Rat Brain Arachidonic Acid Cascade

2014 ◽  
Vol 5 (6) ◽  
pp. 459-467 ◽  
Author(s):  
Stanley I. Rapoport
Keyword(s):  
Bipolar Disorder ◽  
Arachidonic Acid ◽  
Rat Brain ◽  
The Other ◽  
Mood Stabilizers ◽  
Arachidonic Acid Cascade

Is the brain arachidonic acid cascade a common target of drugs used to manage bipolar disorder?

2009 ◽  
Vol 37 (5) ◽  
pp. 1104-1109 ◽  
Author(s):  
Richard P. Bazinet
Keyword(s):  
Bipolar Disorder ◽  
Valproic Acid ◽  
Arachidonic Acid ◽  
Rat Brain ◽  
Bipolar Depression ◽  
Chronic Administration ◽  
Mood Stabilizers ◽  
Arachidonic Acid Cascade ◽  
Brain Phospholipids ◽  
The Brain

Although lithium has been used therapeutically to treat patients with bipolar disorder for over 50 years, its mechanism of action, as well as that of other drugs used to treat bipolar disorder, is not agreed upon. In the present paper, I review studies in unanaesthetized rats using a neuropharmacological approach, combined with kinetic, biochemical and molecular biology techniques, demonstrating that chronic administration of three commonly used mood stabilizers (lithium, valproic acid and carbamazepine), at therapeutically relevant doses, selectively target the brain arachidonic acid cascade. Upon chronic administration, lithium and carbamazepine decrease the binding activity of activator protein-2 and, in turn, the transcription, translation and activity of its arachidonic acid-selective calcium-dependent phospholipase A2 gene product, whereas chronic valproic acid non-competitively inhibits long-chain acyl-CoA synthetase. The net overlapping effects of the three mood stabilizers are decreased turnover of arachidonic acid, but not of docosahexaenoic acid, in rat brain phospholipids, as well as decreased brain cyclo-oxygenase-2 and prostaglandin E2. As an extension of this theory, drugs that are thought to induce switching to mania, especially when administered during bipolar depression (fluoxetine and imipramine), up-regulate enzymes of the arachidonic acid cascade and turnover of arachidonic acid in rat brain phospholipids. Future basic and clinical studies on the arachidonic acid hypothesis of bipolar disorder are warranted.

scholarly journals Valnoctamide, which reduces rat brain arachidonic acid turnover, is a potential non-teratogenic valproate substitute to treat bipolar disorder

2017 ◽  
Vol 254 ◽  
pp. 279-283 ◽  
Author(s):  
Hiren R. Modi ◽  
Kaizong Ma ◽  
Lisa Chang ◽  
Mei Chen ◽  
Stanley I. Rapoport
Keyword(s):  
Bipolar Disorder ◽  
Arachidonic Acid ◽  
Rat Brain

scholarly journals Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?

2008 ◽  
Vol 13 (6) ◽  
pp. 585-596 ◽  
Author(s):  
J S Rao ◽  
H-J Lee ◽  
S I Rapoport ◽  
R P Bazinet
Keyword(s):  
Arachidonic Acid ◽  
Mode Of Action ◽  
Mood Stabilizers ◽  
Arachidonic Acid Cascade ◽  
Common Target

scholarly journals Effects of chronic clozapine administration on markers of arachidonic acid cascade and synaptic integrity in rat brain

2012 ◽  
Vol 222 (4) ◽  
pp. 663-674 ◽  
Author(s):  
Hyung-Wook Kim ◽  
Yewon Cheon ◽  
Hiren R. Modi ◽  
Stanley I. Rapoport ◽  
Jagadeesh S. Rao
Keyword(s):  
Arachidonic Acid ◽  
Rat Brain ◽  
Arachidonic Acid Cascade

scholarly journals Lamotrigine blocks NMDA receptor-initiated arachidonic acid signalling in rat brain: implications for its efficacy in bipolar disorder

2011 ◽  
Vol 15 (07) ◽  
pp. 931-943 ◽  
Author(s):  
Epolia Ramadan ◽  
Mireille Basselin ◽  
Jagadeesh S. Rao ◽  
Lisa Chang ◽  
Mei Chen ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Arachidonic Acid ◽  
Nmda Receptor ◽  
Rat Brain
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