Impaired vasopressin neuromodulation of the lateral septum leads to social behavior deficits in Shank3Bmale mice.

Scientists studied a brain chemical called vasopressin in mice that model autism behaviors. They found these mice had less of this chemical in a brain area that controls social behavior. When researchers increased vasopressin activity using two different pathways, they could improve the mice's social skills and reduce aggression problems. This suggests vasopressin might be a target for future autism treatments.

This preclinical study investigated how the neuropeptide arginine-vasopressin (AVP) affects social behaviors in Shank3B male mice, an established autism spectrum disorder (ASD) model. Researchers found that these mice had reduced AVP inputs from the bed nucleus of the stria terminalis to the lateral septum brain region, correlating with their social deficits. Through targeted manipulations, they demonstrated that AVP promotes both sociability and social aggression via distinct receptor pathways - AVPR1a for sociability and AVPR1b for social aggression. Crucially, selective activation of these receptors successfully rescued the respective behavioral deficits in the autism mouse model, suggesting potential therapeutic targets for addressing social challenges in ASD.

This research identifies vasopressin receptor pathways as potential therapeutic targets for social difficulties in autism. However, extensive human studies are needed before clinical applications. The distinct receptor mechanisms suggest future treatments might be tailored to specific social behavior challenges.

This is a preclinical mouse study with unclear sample sizes. The Shank3B model may not fully represent human autism complexity. Translation from mouse social behaviors to human social functioning requires validation. Long-term effects and safety of receptor manipulations are unknown.

The neuropeptide arginine-vasopressin (AVP) has been repeatedly associated with the autism spectrum disorder (ASD) but the underlying mechanisms remain unclear. As Shank3Bmale mice, a model of ASD, exhibit deficits in sociability and social aggression, we focused on the lateral septum (LS), a brain region involved in the regulation of motivated behaviors and observed reduced AVP inputs from the bed nucleus of the stria terminalis (BNST) to LS. Manipulating AVP release from the BNST to LS of wild-type male mice, we found that AVP promotes both sociability and social aggression. Blocking the vasopressin receptor 1a (AVPR1a) in LS impaired sociability, while blocking the receptor 1b (AVPR1b) disrupted social aggression.

Consequently, selective activation of AVPR1a or AVPR1b rescued the respective behavioral deficits in Shank3Bmale mice. These findings reveal that AVP release in LS modulates two distinct social behaviors via different receptors and highlight a possible strategy to rescue sociability during ASD.