Social behavior deficits following Serotonin 2A Receptor constitutive deletion

SACSON AGOSTINA; MORICI, JUAN F.; GIACHERO MARCELO; BEKINSCHTEIN, P.; WEISSTAUB, NOELIA V.

Buenos Aires

Congreso; http://san2021.saneurociencias.org.ar/wp-content/uploads/2021/12/EBOOK2021.pdf; 2021

SAN

Social behavior (SB) is defined as interactions among individuals that offer mutual benefits and comprisedifferent actions. Deficits in SB are a hallmark of different psychiatric disorders, including autism spectrumdisorders. Changes in 5-HT levels, as well as some activity of key molecules within the system have beenassociated with deficits in SB. Serotonin 2A receptors (5-HT2aR) are one of the main excitatory serotonergicreceptors. Social deficits in humans were associated with 5-HT2aR hypofunction. Interestingly, 5-HT2aRagonists increase social interaction (SI) in humans and animal models suggesting that 5-HT2aR might modulateSB. We used genetically modified male and female mice (htr2a-/-) and their littermates’ controls (htr2a+/+) tostudy the specific role of the receptor in SB. P90 or older animals were exposed to different behavioralparadigms. In the three-chambers SI test htr2a-/- male and female mice show decreased discrimination indexescompared with same sex htr2+/+ mice. Moreover, this deficit was rescued by the genetic restoration of the 5-HT2aR expression in the cortex suggesting a specific role of the receptor in this area. However,pharmacological manipulations in htr2+/+ adult mice before the SI test showed no effect suggesting that 5-HT2aR is not acutely recruited for SB. Taken together, these results suggest that 5-HT2aR has a role in SB andits involvement appears to be due to a developmental or chronic action.