Imaging brain phospholipase A2 activation in awake rats in response to the 5-HT2A/2C agonist (+/-)2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI).
Incorporation coefficients k(*) of intravenously injected [(3)H]arachidonic acid from blood into brain reflect the release from phospholipids of arachidonic acid by receptor-initiated activation of phospholipase A(2) (PLA(2)). In unanesthetized adult rats, 2.5 mg/kg intraperitoneally (i.p.) (+/-)2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI), which is a 5-HT(2A/2C) receptor agonist, has been reported to produce the behavioral changes of what is known as the 5-HT(2) syndrome, but only a few small regional decrements in brain glucose metabolism. In this study, 2.5 mg/kg i.p. DOI, when administered to unanesthetized rats, produced widespread and significant increases, of the order of 60%, in k(*) for arachidonate, particularly in neocortical brain regions reported to have high densities of 5-HT(2A) receptors. The increases could be entirely blocked by chronic pretreatment with mianserin, a 5-HT(2) receptor antagonist. The results suggest that the 5-HT(2) syndrome involves widespread brain activation of PLA(2) via 5-HT(2A) receptors, leading to the release of the second messenger, arachidonic acid. Chronic mianserin, a 5-HT(2) antagonist, prevents this activation.
Qu
Ying
Y
Brain Physiology and Metabolism Section, National Institute of Aging, National Institute of Health, Bethesda, MD 20892, USA. quying@mail.nih.gov
Chang
Lisa
L
Klaff
Justin
J
Balbo
Andrea
A
Rapoport
Stanley I
SI
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects* / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D008297:Male; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D011916:Rats, Inbred F344; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
D000662:Amphetamines; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D010741:Phospholipases A; D054467:Phospholipases A2; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine