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Updated: Sep 27, 2025

An Olfactory Preference Test for Measuring Olfactory Hedonic Biases in Mouse Models of Depression
Published on: July 11, 2025
Antidepressant-like effect of male mating behavior through oxytocin-induced CREB signaling
Hiroaki Matsushita1, Yuya Sasaki2, Aya Yunoki2
1Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan; Nagasaki International University, 2825-7, Huis Ten Bosch, Sasebo 859-3298, Japan.
Abstract:
Male sexual activity reduces the level of depression through oxytocin (OT) release within the brain. In this study, we showed that male mating behavior reduces depression-like behavior through OT-induced cAMP response element binding protein (CREB) signaling in the hippocampus. Moreover, we showed that mating behavior in wild-type (WT) male mice increased CREB phosphorylation in hippocampus, whereas that OT receptor knockout (OTR KO) male mice had no effect on CREB phosphorylation. CREB phosphorylation in hippocampus was also increased after OT induction in hippocampal slices prepared from WT mice. In addition, male mating behavior induced the expression of brain-derived neurotrophic factor (BDNF), which was not observed in OTR KO mice. Antidepressant-like effect of mating behavior had no effect in OTR KO mice. These findings suggest that male sexual activity has antidepressant effects through OT-induced CREB signaling in the hippocampus.
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