Oxytocin receptors within the caudal lateral septum regulate social approach-avoidance, long-term social discrimination, and anxiety-like behaviors in adult male and female rats

OTR signaling promotes social approach or facilitates social avoidance, depending on the brain region involved. The lateral septum plays a critical role in regulating social interactions and memory. We investigated the role of OTR signaling in the caudodorsal lateral septum (LSc.d) in modulating social approach-avoidance behavior, long-term social discrimination memory, and anxiety-like behaviors in adult rats. Local infusion of the selective OTR antagonist L-368,899 (1 μg/0.5 μl) into the LSc.d decreased social approach, increased social vigilance, and reduced long-term social discrimination memory in both sexes. Administration of the biased OTR/Gq agonist carbetocin (0.5 μg/0.5 μl) reduced social approach and long-term social discrimination memory in both sexes, and had anxiogenic effects (increased latency to consume palatable food in test arena) only in males. In contrast, the full OTR agonist TGOT (50 ng/0.5 μl) had no effect on social approach or long-term social discrimination memory, and decreased latency to consume palatable food (anxiolytic effect). The results indicate that the oxytocin system can both promote and inhibit social behaviors depending on the differential activation of G-protein subunits and β-arrestins, as well as the pivotal role of the LS in modulating social and anxiety-like behavior in rats.

Anxiety; Biased agonism; GPCR; Oxytocin receptor; Social behavior.