S-063 | Serotonin 2A receptor plays a sex and time-specific role in social behavior

S-063 | Serotonin 2A receptor plays a sex and time-specific role in social behavior 150 150 SAN 2024 Annual Meeting

Cognition, Behavior, and Memory
Author: Agostina Belén Sacson | Email: agostina.sacson@gmail.com


Agostina Sacson, Marcelo Giachero, Noelia Weisstaub

Laboratorio de Memoria y Cognición Molecular, Instituto de Neurociencia Cognitiva y Traslacional (CONICET-Fundación INECO-Universidad Favaloro), CABA, Argentina

Serotonergic signaling has shown to be a key player in the modulation of social behavior. Specifically, serotonin type 2A receptor (5-HT2AR), known to be involved in a variety of behaviors. It has also been linked to social cognition through the pathophysiology of different psychiatric and neurodevelopmental disorders, and its role in the mechanism of action of so-called “prosocial” drugs. Our lab found that 5-HT2AR knockout (htr2a-/-) mice had reduced discrimination indexes in the three-chambers social interaction test (SIT) compared to wild-type (htr2a+/+) mice. By genetically restoring the expression of 5-HT2AR in the forebrain, mice reached discrimination indexes similar to htr2a+/+. Moreover, acute blockade of 5-HT2AR with MDL 11939 in adult htr2a+/+ mice before the SIT caused an increase in discrimination indexes only in female mice suggesting a sex-specific modulation of the 5-HT2AR in this task. Finally, preliminary results of c-fos expression analysis post-SIT showed differential expression between htr2a+/+ and htr2a-/- mice. In conclusion, these findings suggest that 5-HT2AR plays a role in social behavior, with sex-specific modulation, and highlight the distinct roles of this receptor in social cognition under acute versus developmental manipulations.

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