@article{1f013fa21eff4f14a8d3ff0fa559250d,
title = "Genetic deletion of Rgs12 in mice affects serotonin transporter expression and function in vivo and ex vivo",
abstract = "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-na{\"i}ve 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.",
keywords = "MDMA, RGS12, regulators of G protein signaling, serotonergically modulated behaviors, serotonin transporter",
author = "White, {Allison N.} and Gross, {Joshua D.} and Kaski, {Shane W.} and Trexler, {Kristen R.} and Wix, {Kim A.} and Wetsel, {William C.} and Kinsey, {Steven G.} and Siderovski, {David P.} and Vincent Setola",
note = "Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Funding for these studies was supported in part by the WVU Department of Physiology and Pharmacology{\textquoteright}s EJ Van Liere Endowed Medicine Professorship (to DPS), and R03 DA039335 (to SGK). ANW had predoctoral support from the WVU Behavioral and Biomedical Sciences T32 training grant (NIH T32 GM132494). JDG and SWK each had early predoctoral support from NIH T32 GM081741 and subsequent independent support from a NIDA predoctoral fellowship (NIH F31 DA043331) and a NIDA MD/PhD combined degree fellowship (NIH F30 DA044711), respectively. Some of the behavioral equipment and software at the Duke University Mouse Behavioral and Neuroendocrine Analysis Core Facility was purchased by a grant from the North Carolina Biotechnology Center. Funding Information: We thank Dr Ramona Rodriguiz (Assistant Director, Duke University Mouse Behavioral and Neuroendocrine Analysis Core Facility) for providing training and advice on EZM and sociability tests. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Funding for these studies was supported in part by the WVU Department of Physiology and Pharmacology{\textquoteright}s EJ Van Liere Endowed Medicine Professorship (to DPS), and R03 DA039335 (to SGK). ANW had predoctoral support from the WVU Behavioral and Biomedical Sciences T32 training grant (NIH T32 GM132494). JDG and SWK each had early predoctoral support from NIH T32 GM081741 and subsequent independent support from a NIDA predoctoral fellowship (NIH F31 DA043331) and a NIDA MD/PhD combined degree fellowship (NIH F30 DA044711), respectively. Some of the behavioral equipment and software at the Duke University Mouse Behavioral and Neuroendocrine Analysis Core Facility was purchased by a grant from the North Carolina Biotechnology Center. Publisher Copyright: {\textcopyright} The Author(s) 2020.",
year = "2020",
month = dec,
doi = "10.1177/0269881120944160",
language = "English",
volume = "34",
pages = "1393--1407",
journal = "Journal of Psychopharmacology",
issn = "0269-8811",
publisher = "SAGE Publications Ltd",
number = "12",
}