Mechanisms Of Action Of Lithium And Other Drugs In Bipol

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1. Using our in vivo fatty acid method (AG000134-20 BPMS), we demonstrated that chronic lithium administration to rats enhanced brain cholinergic muscarinic receptor-mediated activation of PLA2, to release the second messenger, AA from membrane phospholipids. Such enhancement is consistent with lithium?s reported ability to reduce the convulsant threshold to cholinomimetics in rodents and the reported therapeutic efficacy of cholinomimetics in human bipolar disorder. 2. With our fatty acid method (AG000134-20 BPMS), we imaged serotonergic (5-HT) signal transduction involving arachidonic acid (AA) in awake rats. Acute administration of the 5-HT2A/2C receptor agonist, (+-)-2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI), or of fluoxetine (Prozac, an antidepressant that increases 5-HT in the synaptic cleft), stimulated brain incorporation of intravenously-injected radiolabeled AA, a marker of phospholipase A2 (PLA2) activation. The effect was blocked by pre-administration of a 5-HT2A/2C receptor antagonist. These results are consistent with fluoxetine being effective in depression by increasing AA release from membrane phospholipids through the 5-HT2A/2C - mediated activation of PLA2.