5-HT2A/2C receptor signaling via phospholipase A2 and arachidonic acid is attenuated in mice lacking the serotonin reuptake transporter

Abstract

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.

A Nonlinear Relationship between Cerebral Serotonin Transporter and 5-HT2AReceptor Binding: AnIn VivoMolecular Imaging Study in Humans

“…SERT knock-out mice have a sixfold increase in extracellular 5-HT (Bengel et al, 1998), and, in these mice, a 42% decrease is seen in the cortical but not in the striatal 5-HT 2A receptor density (Rioux et al, 1999). Consistent with this observation, pharmacological stimulation with a 5-HT 2A receptor agonist was associated with a marked attenuation of the head-twitch response and in phospholipase A2 signaling in SERT knock-out compared with SERT overexpressing mice (Qu et al, 2005). Similarly, in SERT overexpressing mice with decreased extracellular 5-HT levels, increased functional sensitivity of the 5-HT 2A receptor was found; 5-HT 2A receptor agonist stimulation induced a greater increase in both c-Fos and Arc mRNA expression in cortical brain regions and more head twitches compared with wild-type mice (Jennings et al, 2008), although the authors were unable to demonstrate significantly increased 5-HT 2A receptor binding.…”

Psychedelics

“…The authors cite five earlier studies (Table 7 in Dougherty and Aloyo, 2011) that all reported similar findings, in which changes in 5-HT 2A receptor density were correlated with changes in the number of HTRs. Qu et al (2005) used PLA 2 as a measure of regional brain activation in SERT KO mice (SERT 2/2 ) and their 316 Nichols littermate controls (WT; SERT +/+ ). Unanesthetized mice were injected intravenously with [ 3 H]AA and the regional coefficient of incorporation k* of AA from plasma into phospholipids of individual brain regions was subsequently measured by quantitative autoradiography in 71 different brain regions.…”

Lack of the serotonin transporter in mice reduces locomotor activity and leads to gender-dependent late onset obesity

“…27,28 As antagonism to 5-HT2A receptors 29,30 increases adiponectin levels, this chain of events may protect obese 5-HTT mice from the full metabolic syndrome. Although the limitations of germline ko models compared with inducible ko strategies have to be considered, 5-HTT ko mice differ from previously described models of late-onset obesity and may serve as a paradigm for a different subset of obese humans.…”