Effects of the Mouse Estrous Cycle on Neuropeptide S Receptor-Mediated Behaviors.

The neuropeptide S receptor (NPSR) is a G protein-coupled receptor that has been implicated in various disease states, such as anxiety and post-traumatic stress disorder, and has shown promise as a target for the treatment of anxiety. Central brain administration of Neuropeptide S (NPS) in mice produces anxiolytic-like effects, hyperlocomotion, and memory enhancement. Since current anxiety drugs cause undesirable side effects, development of more efficacious drugs is important. However, research into this system has been conducted solely in male rodents, despite females showing a higher prevalence for anxiety disorders. The current study investigated whether NPS-mediated behavioral phenotypes seen in males translate to females, and whether they are affected by estrous cycle stage. Female C57BL/6 mice were intracerebroventricularly (ICV) cannulated and underwent various behavioral paradigms. Estrous cycle stage was determined through examination of vaginal cytology. Consistent with findings in male mice, NPS-treated females displayed hyperlocomotion. Additionally, NPS-treated females displayed anxiolytic-like behaviors, but preliminary data suggests this effect is contingent on different phases of the estrous cycle. These results indicate that the NPSR could be a viable pharmaceutical target to treat anxiety disorders, as the anxiolytic phenotype is present in both sexes. However, in females, these effects seem to be dependent on the stage of the estrous cycle.