Imaging of brain serotonergic neurotransmission involving phospholipase A2 activation and arachidonic acid release in unanesthetized rats.
In vitro studies have shown that 5-HT2 receptors can be coupled via G-proteins to phospholipase A2 (PLA2) activation, releasing arachidonic acid from phospholipids. To examine this signaling pathway in brain, we developed an in vivo method to image regional brain PLA2 activation in unanesthetized rats given different types of serotonergic drugs. Increased arachidonate incorporation from plasma, in response to drug-induced PLA2-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 A2. The detailed method is described.
Qu
Ying
Y
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Building 10, Rm. 6N202, Bethesda, MD 20892, USA. yqu1@prdus.jnj.com
Chang
Lisa
L
Klaff
Justin
J
Seeman
Ruth
R
Balbo
Andrea
A
Rapoport
Stanley I
SI
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001345:Autoradiography; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D003952:Diagnostic Imaging; D004789:Enzyme Activation; D007091:Image Processing, Computer-Assisted; D008297:Male; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D011916:Rats, Inbred F344; D012701:Serotonin / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D014018:Tissue Distribution
D016718:Arachidonic Acid; D012701:Serotonin; D010741:Phospholipases A; D054467:Phospholipases A2