title: 5-HT2A/2C receptor signaling via phospholipase A2 and arachidonic acid is attenuated in mice lacking the serotonin reuptake transporter.
abstract: METHODS
  The serotonin reuptake transporter (SERT) helps to regulate brain serotonergic transmission and is the target of some antidepressants. To further understand SERT function, we measured a marker of regional brain phospholipase A2 (PLA2) activation in SERT knockout mice (SERT-/-) and their littermate controls (SERT+/+).
  
  
  METHODS
  Following administration of 1.5 mg/kg s.c. (+/-)-2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI), a 5-HT(2A/2C) receptor agonist, to unanesthetized mice injected intravenously with radiolabeled arachidonic acid (AA), PLA2 activation, represented as the regional incorporation coefficient k* of AA, was determined with quantitative autoradiography in each of 71 brain regions.
  
  
  RESULTS
  In SERT+/+ mice, DOI significantly increased k* in 27 regions known to have 5-HT(2A/2C) receptors, including the frontal, motor, somatosensory, pyriform and cingulate cortex, white matter, nucleus accumbens, caudate putamen, septum, CA1 of hippocampus, thalamus, and hypothalamus. In contrast, DOI did not increase k* significantly in any brain region of SERT-/- mice. Head twitches following DOI, which also were measured, were robust in SERT+/+ mice but were markedly attenuated in SERT-/- mice.
  
  
  CONCLUSIONS
  These results show that a lifelong elevation of the synaptic 5-HT concentration in SERT-/- mice leads to downregulation of 5-HT(2A/2C) receptor-mediated PLA2 signaling via AA and of head twitches, in response to DOI.
authors.affiliation: Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Building 9, Room 1S128, Bethesda, MD, 20892, USA. yqu1@prdus.jnj.com
authors.forename: Ying
authors.initials: Y
authors.lastname: Qu
authors.forename: Nelly
authors.initials: N
authors.lastname: Villacreses
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Murphy
authors.forename: Stanley I
authors.initials: SI
authors.lastname: Rapoport
mesh_terms: D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000096:biosynthesis*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010741:Phospholipases A / Q000096:biosynthesis*; D054467:Phospholipases A2; D011877:Radionuclide Imaging; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology*; D058826:Serotonin 5-HT2 Receptor Agonists; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: D000662:Amphetamines; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine