Role of 5-HT2A Receptor in Social Cognition in Mice

Abstract

The serotonergic system and more precisely the serotonin type 2Areceptor (5-HT2AR) is involved in a wide variety of cognitive and emotionalfunctions. In recent studies, it has been found that 5-HT2AR participates inthe prosocial effects of certain drugs. Moreover, the social cognitiveimpairments observed in different psychiatric disorders, such as schizophreniaand Asperger syndrome, have been associated with a hypofunction of the 5-HT2AR.However, the mechanisms underlying this phenotype remain unclear. In thepresent study we analyzed the role of 5-HT2AR in social preference (SP) using agenetically modified mouse model that presents a constitutive depletion ofthe5-HT2AR (KO) compared with their wild type mates (WT). For this purpose weperformed a three-chamber sociability test. We also explore how SP can beaffected by an increased level of serotonin in the central nervous system viachronic administration of fluoxetine. We observed that both male and female KOmice had a lower social preference compared to WT. Thus, the chronicadministration of fluoxetine increased social preference only in WT mice. Theseresults suggest that the serotonergic system could be involved in SP and thatits participation could mediated at least partially by 5-HT2AR.