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• W2912194297 endingPage "e0211239" @default.
• W2912194297 startingPage "e0211239" @default.
• W2912194297 abstract "Serotonin-1B receptors (5-HT1BRs) modulate perseverative behaviors and prepulse inhibition (PPI) in humans and mice. These inhibitory G-protein-coupled receptors signal through a canonical G-protein-coupled pathway that is modulated by GSK-3β, and a noncanonical pathway mediated by the adaptor protein β-arrestin2 (Arrb2). Given the development of biased ligands that differentially affect canonical versus noncanonical signaling, we examined which signaling pathway mediates 5-HT1BR agonist-induced locomotor perseveration and PPI deficits, behavioral phenotypes observed in both obsessive-compulsive disorder (OCD) and autism spectrum disorder (ASD). To assess the role of canonical 5-HT1BR signaling, mice received acute pretreatment with a GSK-3 inhibitor (SB216763 or AR-A014418) and acute treatment with the 5-HT1A/1B receptor agonist RU24969 prior to assessing perseverative locomotor behavior in the open field, and PPI. To determine the role of noncanonical 5-HT1BR signaling, Arrb2 wild-type (WT), heterozygous (HT), and knockout (KO) mice received acute RU24969 treatment prior to behavioral testing. GSK-3 inhibition increased locomotor perseveration overall, and also failed to influence the RU24969-induced perseverative locomotor pattern in the open field. Yet, GSK-3 inhibition modestly reduced RU24969-induced PPI deficits. On the other hand, Arrb2 HT and KO mice showed reduced locomotion and no changes in perseveration overall, in addition to modest reductions in RU24969-induced locomotion and PPI deficits. In conclusion, our data do not support use of either GSK-3 inhibitors or β-arrestin2 inhibition in treatment of perseverative behaviors." @default.
• W2912194297 created "2019-02-21" @default.
• W2912194297 creator A5062760806 @default.
• W2912194297 creator A5076408885 @default.
• W2912194297 date "2019-02-05" @default.
• W2912194297 modified "2023-10-10" @default.
• W2912194297 title "Dissecting the roles of β-arrestin2 and GSK-3 signaling in 5-HT1BR-mediated perseverative behavior and prepulse inhibition deficits in mice" @default.
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• W2912194297 doi "https://doi.org/10.1371/journal.pone.0211239" @default.
• W2912194297 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6363181" @default.
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