Citalopram attenuates social behavior deficits in the BTBR T+Itpr3tf/J mouse model of autism

Autism spectrum disorder (ASD) is diagnosed by two core symptoms: impaired social communication and the presence of repetitive, stereotyped behaviors and/or restricted interests. Alterations in serotonergic signaling are involved in the genesis of ASD. Selective serotonin reuptake inhibitors (SSRIs) have been reported to reduce repetitive behaviors and rescue social deficits in ASD mouse models and patients. In the present study, we examined the potential of citalopram (a representative selective serotonin reuptake inhibitor) on sociability and repetitive behaviors in the BTBR T(+)Itpr3(tf)/J (BTBR) mouse model of ASD. We found that the deficits of sociability in the BTBR mice were reversed by a 20 mg/kg dose of citalopram treatment without any adverse effects on locomotor activity or anxiety level. In addition, both high (20 mg/kg) and low (10 mg/kg) doses decreased the repetitive behavior of marble burying but did not affect self-grooming behavior. Furthermore, both doses were shown to have antidepressant-like activity in both the B6 and the BTBR mice in the tail suspension test. Taken together, these findings further demonstrate that citalopram can alleviate behavioral abnormalities in the BTBR autism model and lend support to the hypothesis that SSRIs may be potential therapeutic drugs for the treatment of behavioral dysfunctions in ASD.