Vortioxetine Reduces Marble Burying but Only Transiently Enhances Social Interaction Preference in Adult Male BTBR T + Itpr3 tf /J Mice.

Vortioxetine is a multimodal antidepressant with agonist activity at serotonin (5-HT) and 5-HT receptors that blocks the 5-HT transporter (SERT). Previously in male BTBR TItpr3/J (BTBR) mice the 5-HT agonist buspirone and SERT blocker fluoxetine enhanced social interaction but didn't reduce marble burying. We hypothesized vortioxetine, through SERT and 5-HT could improve BTBR sociability, and via 5-HT could reduce burying better than a selective SERT blocker. Vortioxetine (5-10 mg/kg) or sertraline (2 mg/kg) were administered 50 min pre-sociability and 75 min pre-marble burying tests. Vortioxetine (10 mg/kg) occupancy (%) was 84 ± 1 for SERT, 31 ± 12 for 5-HT and 80 ± 5 for 5-HT in brain at 110 min post-injection, and serum oxytocin was 24% lower (p < 0.01) in vortioxetine-treated mice. Vortioxetine enhanced social sniffing, whereas sertraline enhanced overall sociability. However, the vortioxetine-induced increase in social sniffing was transient, as it was lost with 30 - 60 min pre-test delays in subsequent experiments. Vortioxetine, and sertraline reduced BTBR marble burying. Based on vortioxetine occupancy SERT and/or 5-HT are more likely to underlie these effects than 5-HT occupancy. Overall, vortioxetine has great potential for suppressing restrictive-repetitive behaviors, but appears less promising as a sociability enhancer.