Genetic deletion ofRgs12in mice affects serotonin transporter expression and functionin vivoandex vivo
| Autor: | Joshua D Gross, Kristen R Trexler, Vincent Setola, William C. Wetsel, Shane W Kaski, Allison N White, Kim Wix, Steven G. Kinsey, David P. Siderovski |
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| Rok vydání: | 2020 |
| Předmět: |
Male
N-Methyl-3 4-methylenedioxyamphetamine Article Mice 03 medical and health sciences chemistry.chemical_compound Serotonin Agents 0302 clinical medicine Regulator of G protein signaling In vivo Animals Pharmacology (medical) Social Behavior Neurotransmitter Receptor Serotonin transporter 030304 developmental biology G protein-coupled receptor Mice Knockout Serotonin Plasma Membrane Transport Proteins Pharmacology 0303 health sciences Behavior Animal biology Cell biology Mice Inbred C57BL Psychiatry and Mental health chemistry biology.protein Locomotion RGS Proteins 030217 neurology & neurosurgery Ex vivo Function (biology) |
| Zdroj: | J Psychopharmacol |
| ISSN: | 1461-7285 0269-8811 |
| Popis: | Background:Regulator of G protein Signaling (RGS) proteins inhibit G protein-coupled receptor (GPCR) signaling, including the signals that arise from neurotransmitter release. We have shown that RGS12 loss diminishes locomotor responses of C57BL/6J mice to dopamine transporter (DAT)-targeting psychostimulants. This diminution resulted from a brain region-specific upregulation of DAT expression and function in RGS12-null mice. This effect on DAT prompted us to investigate whether the serotonin transporter (SERT) exhibits similar alterations upon RGS12 loss in C57BL/6J mice.Aims:Does RGS12 loss affect (a) hyperlocomotion to the preferentially SERT-targeting psychostimulant 3,4-methylenedioxymethamphetamine (MDMA), (b) SERT expression and function in relevant brain regions, and/or (c) serotonergically modulated behaviors?Methods:Open-field and spontaneous home-cage locomotor activities were quantified. 5-HT, 5-HIAA, and SERT levels in brain-region homogenates, as well as SERT expression and function in brain-region tissue preparations, were measured using appropriate biochemical assays. Serotonergically modulated behaviors were assessed using forced swim and tail suspension paradigms, elevated plus and elevated zero maze tests, and social interaction assays.Results:RGS12-null mice displayed no hyperlocomotion to 10 mg/kg MDMA. There were brain region-specific alterations in SERT expression and function associated with RGS12 loss. Drug-naïve RGS12-null mice displayed increases in both anxiety-like and anti-depressive-like behaviors.Conclusion:RGS12 is a critical modulator of serotonergic neurotransmission and serotonergically modulated behavior in mice; lack of hyperlocomotion to low dose MDMA in RGS12-null mice is related to an alteration of steady-state SERT expression and 5-HT uptake. |
| Databáze: | OpenAIRE |
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