Abstract
In vitro studies have shown that 5-HT 2 receptors can be coupled via G-proteins to phospholipase A 2 (PLA 2) activation, releasing arachidonic acid from phospholipids. To examine this signaling pathway in brain, we developed an in vivo method to image regional brain PLA 2 activation in unanesthetized rats given different types of serotonergic drugs. Increased arachidonate incorporation from plasma, in response to drug-induced PLA 2-activation, can be quantified with autoradiography, following the intravenous injection of radiolabeled arachidonate. For example, a 5-HT 2A/2C receptor agonist, (±)-2,5-dimethoxy-4-iodophenyl-2-aminopropane, produced widespread increases in incorporation of labeled arachidonate by directly binding to 5-HT 2A/2C receptors. Fluoxetine, a selective serotonin reuptake inhibitor, selectively increased incorporation of arachidonic acid by increasing 5-HT availability in the synaptic cleft and thus indirectly activating phospholipase A 2. The detailed method is described.
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