Regulation of social behaviour via oxytocin receptor signaling in the caudodorsal lateral septum in Long-Evans male and female rats

Abstract

The oxytocin receptor (OTR), a class A G-protein coupled receptor, is highly expressed in the lateral septum (LS), a brain region that regulates social behaviors in rodents. This thesis investigates whether OTRs within the LS modulate social approach-avoidance behavior, acquisition of long-term social recognition memory, and anxiety-like behavior in adult male and female rats. In the first experiment, L-368, 899, a selective OTR antagonist, was infused locally into the caudodorsal lateral septum (LSc.d), resulting in the attenuation of social approach, enhancement of social vigilance, and reduction in social novelty preference in male and female rats, with no effect on locomotion. In the second experiment, carbetocin, a biased OTR/Gq agonist, was locally delivered into the LSc.d, leading to reduced social approach and social novelty preference (a measure of social memory), with no effect on social vigilance or locomotion. Intriguingly, carbetocin increased latency to consumption of a highly palatable food only in male rats in the novelty-induced hypophagia test, indicating the sex-specific anxiogenic effects of the OTR/Gq signaling pathway in the region. In the third experiment, a selective full agonist of the OTR, (Thr4,Gly7)-Oxytocin, was infused into the LSc.d of male rats, resulting in a slight, but non-significant increase in social approach. Unlike the antagonist and the biased agonist, (Thr4,Gly7)-Oxytocin-treated rats showed social novelty preference 24 h after familiarization. Moreover, (Thr4,Gly7)-Oxytocin decreased latency to consumption of a highly palatable food compared to vehicle-treated rats, suggesting anxiolytic effects of the OTR full agonism. In conclusion, the findings suggest that OTR signaling in the LSc.d regulates social approach-avoidance, acquisition of social recognition memory and anxiety-like behavior depending on the activation of a specific upstream signaling arm of the receptor. I demonstrated that the OTR/Gq signaling pathway within the LSc.d promotes social avoidance in both sexes and triggers anxiogenic effects only in males, contrasting with the effects induced by the full agonism of the receptor

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This paper was published in Brock University Digital Repository.

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