Imaging Brain Phospholipase A2 Activation in Awake Rats in Response to the 5-HT2A/2C Agonist (±)2,5-Dimethoxy-4-Iodophenyl-2-Aminopropane (DOI)
Y. Qu, Lisa Chang, J. Klaff, A. Balbo, S. Rapoport
Neuropsychopharmacology February 1, 2003 DOI: 10.1038/sj.npp.1300022 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Unanesthetized adult rats |
| Interventions | DOI mianserin |
| Dose | 2.5 mg/kg i.p. DOI |
| Key findings | DOI at 2.5 mg/kg i.p. produced widespread increases of about 60% in arachidonic acid incorporation coefficient in neocortical brain regions, which were entirely blocked by chronic mianserin pretreatment. |
Abstract
Incorporation coefficients k* of intravenously injected [3H]arachidonic acid from blood into brain reflect the release from phospholipids of arachidonic acid by receptor-initiated activation of phospholipase A2 (PLA2). In unanesthetized adult rats, 2.5 mg/kg intraperitoneally (i.p.) (±)2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI), which is a 5-HT2A/2C receptor agonist, has been reported to produce the behavioral changes of what is known as the 5-HT2 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-HT2A receptors. The increases could be entirely blocked by chronic pretreatment with mianserin, a 5-HT2 receptor antagonist. The results suggest that the 5-HT2 syndrome involves widespread brain activation of PLA2 via 5-HT2A receptors, leading to the release of the second messenger, arachidonic acid. Chronic mianserin, a 5-HT2 antagonist, prevents this activation.