PMID- 32842837
OWN - NLM
STAT- MEDLINE
DCOM- 20211104
LR  - 20211111
IS  - 1461-7285 (Electronic)
IS  - 0269-8811 (Print)
IS  - 0269-8811 (Linking)
VI  - 34
IP  - 12
DP  - 2020 Dec
TI  - Genetic deletion of Rgs12 in mice affects serotonin transporter expression and 
      function in vivo and ex vivo.
PG  - 1393-1407
LID - 10.1177/0269881120944160 [doi]
AB  - 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-naive 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.
FAU - White, Allison N
AU  - White AN
AD  - Department of Neuroscience, West Virginia University, Morgantown, USA.
FAU - Gross, Joshua D
AU  - Gross JD
AD  - Department of Neuroscience, West Virginia University, Morgantown, USA.
FAU - Kaski, Shane W
AU  - Kaski SW
AD  - Department of Neuroscience, West Virginia University, Morgantown, USA.
AD  - Department of Behavioral Medicine and Psychiatry, West Virginia University, 
      Morgantown, USA.
FAU - Trexler, Kristen R
AU  - Trexler KR
AD  - Department of Neuroscience, West Virginia University, Morgantown, USA.
AD  - Department of Psychology, West Virginia University, Morgantown, USA.
FAU - Wix, Kim A
AU  - Wix KA
AD  - Department of Neuroscience, West Virginia University, Morgantown, USA.
FAU - Wetsel, William C
AU  - Wetsel WC
AD  - Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, 
      Durham, USA.
AD  - Departments of Cell Biology and Neurobiology, Duke University Medical Center, 
      Durham, USA.
FAU - Kinsey, Steven G
AU  - Kinsey SG
AD  - Department of Neuroscience, West Virginia University, Morgantown, USA.
AD  - Department of Psychology, West Virginia University, Morgantown, USA.
FAU - Siderovski, David P
AU  - Siderovski DP
AUID- ORCID: 0000-0002-0688-8210
AD  - Department of Neuroscience, West Virginia University, Morgantown, USA.
FAU - Setola, Vincent
AU  - Setola V
AD  - Department of Neuroscience, West Virginia University, Morgantown, USA.
AD  - Department of Behavioral Medicine and Psychiatry, West Virginia University, 
      Morgantown, USA.
LA  - eng
GR  - F30 DA044711/DA/NIDA NIH HHS/United States
GR  - T32 GM081741/GM/NIGMS NIH HHS/United States
GR  - T32 GM132494/GM/NIGMS NIH HHS/United States
GR  - R03 DA039335/DA/NIDA NIH HHS/United States
GR  - F31 DA043331/DA/NIDA NIH HHS/United States
GR  - R01 DA048153/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200825
PL  - United States
TA  - J Psychopharmacol
JT  - Journal of psychopharmacology (Oxford, England)
JID - 8907828
RN  - 0 (RGS Proteins)
RN  - 0 (RGS12 protein, mouse)
RN  - 0 (Serotonin Agents)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Slc6a4 protein, mouse)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/drug effects/*physiology
MH  - Locomotion/drug effects/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage/*pharmacology
MH  - RGS Proteins/genetics/*physiology
MH  - Serotonin Agents/administration & dosage/*pharmacology
MH  - Serotonin Plasma Membrane Transport Proteins/*metabolism
MH  - Social Behavior
PMC - PMC8576640
MID - NIHMS1749362
OTO - NOTNLM
OT  - MDMA
OT  - RGS12
OT  - regulators of G protein signaling
OT  - serotonergically modulated behaviors
OT  - serotonin transporter
EDAT- 2020/08/28 06:00
MHDA- 2021/11/05 06:00
PMCR- 2021/11/09
CRDT- 2020/08/27 06:00
PHST- 2020/08/28 06:00 [pubmed]
PHST- 2021/11/05 06:00 [medline]
PHST- 2020/08/27 06:00 [entrez]
PHST- 2021/11/09 00:00 [pmc-release]
AID - 10.1177/0269881120944160 [doi]
PST - ppublish
SO  - J Psychopharmacol. 2020 Dec;34(12):1393-1407. doi: 10.1177/0269881120944160. Epub 
      2020 Aug 25.