I.c.v. administration of orexin-A induces an antidepressive-like effect through hippocampal cell proliferation

Involvement of Neuropeptide Y Signaling in the Antidepressant-Like Effect and Hippocampal Cell Proliferation Induced by Kososan, a Kampo Medicine, in the Stress-Induced Depression-Like Model Mice

“…However, these results do not mean that the mediation of NPY signaling is independent of that of OX-A signaling for the kososan-induced antidepressant-like effect, because we previously demonstrated that OX-A signaling is necessary for hippocampal upregulation of NPY levels. 46,50) It has also been reported that NPY neurons in the arcuate nucleus of the hypothalamus are directly activated by OX-A via OXR1. 59) These results, together with those of our previous study, suggest that the hippocampal NPY system does not regulate the OX-A system in the LHA, but that the NPY system could be modulated by OX-A signaling through OXR1 in the hypothalamic-hippocampal neural network.…”

“…46) So far, it has been assumed that the mediation of hypothalamic NPY appears not to be required for the onset of an antidepressantlike effect. The characteristic difference in the distribution of NPY between the hippocampus and the hypothalamus also may be based on region-specific actions of NPY.…”

“…[41][42][43] Moreover, OX-A signaling is associated with the onset of antidepressant-like activity in mice. [44][45][46] These evidences suggest that NPY and OX-A could be key mediators in the pathology of depression and in antidepressant-like effects.…”

“…[41][42][43] Moreover, OX-A signaling is associated with the onset of antidepressant-like activity in mice. [44][45][46] These evidences suggest that NPY and OX-A could be key mediators in the pathology of depression and in antidepressant-like effects.Kososan, a Kampo (Japanese herbal) medicine (Xiang-Su-San in Chinese), is composed of five herbs (Cyperi Rhizoma, Perillae Herba, Aurantii Nobilis Pericarpium, Glycyrrhizae Radix, and Zingiberis Rhizoma) and is clinically applied in the treatment of depression-like symptoms associated with the initial stage of the common cold, anorexia, food-related allergic urticaria, irritable bowel syndrome, chronic fatigue syndrome, insomnia, and autonomic imbalance. It has been also clinically suggested that kososan can alleviate depression induced by interferon (IFN)-α therapy for hepatitis C. 47) Our previous studies using two animal models of depression, stress-and IFN-α-induced depressionlike model mice, demonstrated that the oral administration of kososan leads to an antidepressant-like effect by normalizing…”

International Union of Basic and Clinical Pharmacology. LXXXVI. Orexin Receptor Function, Nomenclature and Pharmacology

“…The activation of orexin-secreting and orexin receptor-expressing neurons in response to stress and orexin activation of stress-related systems, including norepinephrine, dopamine, and CRF, may point to a possible role in PTSD and depression (Berridge et al, 2010). OX-A administration was reported to reduce immobility in the rat forced-swim test and increased hippocampal neurogenesis, with pretreatment of SB-334867 blocking these effects (Ito et al, 2008). Lutter et al (2008) showed that intact orexin signaling was necessary for the efficacy of caloric restriction in a mouse model of depression.…”