Dataset Information

Regulation of social hierarchy learning by serotonin transporter availability.

ABSTRACT: Learning one's status in a group is a fundamental process in building social hierarchies. Although animal studies suggest that serotonin (5-HT) signaling modulates learning social hierarchies, direct evidence in humans is lacking. Here we determined the relationship between serotonin transporter (SERT) availability and brain systems engaged in learning social ranks combining computational approaches with simultaneous PET-fMRI acquisition in healthy males. We also investigated the link between SERT availability and brain activity in a non-social control condition involving learning the payoffs of slot machines. Learning social ranks was modulated by the dorsal raphe nucleus (DRN) 5-HT function. BOLD ventral striatal response, tracking the rank of opponents, decreased with DRN SERT levels. Moreover, this link was specific to the social learning task. These findings demonstrate that 5-HT plays an influence on the computations required to learn social ranks.

SUBMITTER: Janet R

PROVIDER: S-EPMC9630526 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Regulation of social hierarchy learning by serotonin transporter availability.

Janet Remi R Ligneul Romain R Losecaat-Vermeer Annabel B AB Philippe Remi R Bellucci Gabriele G Derrington Edmund E Park Soyoung Q SQ Dreher Jean-Claude JC

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20220809 13

Learning one's status in a group is a fundamental process in building social hierarchies. Although animal studies suggest that serotonin (5-HT) signaling modulates learning social hierarchies, direct evidence in humans is lacking. Here we determined the relationship between serotonin transporter (SERT) availability and brain systems engaged in learning social ranks combining computational approaches with simultaneous PET-fMRI acquisition in healthy males. We also investigated the link between SE ...[more]

PMID: 35945275

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Project description:IntroductionHypercholesterolemia is associated with increased inflammation and impaired serotonin neurotransmission, potentially contributing to depressive symptoms. However, the role of statins, particularly pitavastatin, in modulating serotonin transporter (SERT) function within this context remains underexplored. This study aimed to investigate whether pitavastatin counteracts the neurobiological effects of hypercholesterolemia.MethodsLow-density lipoprotein receptor knockout (LDLR-/-) mice on a C57BL/6 background were assigned to three groups: a control group fed a standard chow diet, a group fed a high-fat diet (HFD), and a third group fed a high-fat diet supplemented with pitavastatin (HFD + Pita). We evaluated the effects of HFD with or without pitavastatin on lipid profiles, inflammatory markers, and SERT availability using small-animal positron emission tomography (PET) scans with the radioligand 4-[18F]-ADAM over a 20-week period.ResultsPitavastatin treatment in HFD-fed mice significantly reduced both total cholesterol and LDL cholesterol levels in HFD-fed mice compared to those on HFD alone. Elevated inflammatory markers such as IL-1α, MCP-1/CCL2, and TNF-α in HFD mice were notably decreased in the HFD + Pita group. PET scans showed reduced SERT availability in the brains of HFD mice; however, pitavastatin improved this in brain regions associated with mood regulation, suggesting enhanced serotonin neurotransmission. Additionally, the sucrose preference test showed a trend towards increased preference in the HFD + Pita group compared to the HFD group, indicating a potential reduction in depressive-like behavior.ConclusionOur findings demonstrate that pitavastatin not only lowers cholesterol and reduces inflammation but also enhances SERT availability, suggesting a potential role in alleviating depressive symptoms associated with hypercholesterolemia. These results highlight the multifaceted benefits of pitavastatin, extending beyond its lipid-lowering effects to potentially improving mood regulation and neurotransmitter function.

Dataset Information

Regulation of social hierarchy learning by serotonin transporter availability.

Publications

Regulation of social hierarchy learning by serotonin transporter availability.

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