Antidepressant-like effect of male mating behavior through oxytocin-induced CREB signaling.

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.

Oxytocin and Stress: Neural Mechanisms, Stress-Related Disorders, and Therapeutic Approaches.

Clinical reports show that oxytocin (OT) is related to stress-related disorders such as depression, anxiety disorder, and post-traumatic stress disorder. Two key structures in the brain should be paid special attention with regard to stress regulation, namely, the hypothalamus and the hippocampus. The former is the region for central command for most, if not all, of the major endocrine systems, and the latter takes a key position in the regulation of mood and anxiety. There are extensive neural projections between the two structures, and both are functionally intertwined. The hypothalamus projects OTergic neurons to the hippocampus, and the latter possesses high levels of OT receptors. The hippocampus also regulates the secretion of glucocorticoids, a major group of stress hormones. Excessive levels of glucocorticoids in chronic stress cause atrophy of the hippocampus, whereas OT has been shown to protect hippocampal neurons from the toxic effects of glucocorticoids. In this article, we discuss how neural and endocrine mechanisms interplay in stress regulation, with an emphasis on the role of OT, as well as its therapeutic potential in the treatment of stress-related disorders.

Oxytocin Inhibits Corticosterone-induced Apoptosis in Primary Hippocampal Neurons.

Stress is an adaptive and coordinated response to endogenous or exogenous stressors that pose an unpleasant and aversive threat to an individual's homeostasis and wellbeing. Glucocorticoids, corticosterone (CORT) in rodents and cortisol in humans, are adrenal steroids which are released in response to stressful stimuli. Although they help individuals to cope with stress, their overexposure in animals has been implicated in hippocampal dysfunction and neuronal loss. Oxytocin (OT) plays an active role in adaptive stress-related responses and protects hippocampal synaptic plasticity and memory during stress. In this study, we showed that OT protects primary mouse hippocampal neurons from CORT-induced apoptosis. OT receptors (OTR) were expressed in primary mouse hippocampal neurons and glial cells. CORT induced apoptosis in hippocampal neurons, but had no effect on apoptosis in glial cells. OT inhibited CORT-induced apoptosis in primary hippocampal neurons. OT was unable to protect primary hippocampal neurons prepared from OTR KO mice from CORT-induced apoptosis. These results indicate that OT has inhibitory effects on CORT-induced neuronal death in primary hippocampal neurons via acting on OTR. The findings suggest a therapeutic potential of OT in the treatment of stress-related disorders.