¹Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA

Correspondence: Ying Qu, Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Building 10, Room 6N202, Bethesda, MD 20892, USA. Tel: +1 301 594 3134; Fax: +1 301 402 0074; E-mail: quying@mail.nih.gov

Received 10 January 2002; Revised 30 May 2002; Accepted 3 June 2002.

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-HT_2A/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-HT_2A 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-HT_2A receptors, leading to the release of the second messenger, arachidonic acid. Chronic mianserin, a 5-HT₂ antagonist, prevents this activation.