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

• Published in: Biological & pharmaceutical bulletin Vol. 35; no. 10; pp. 1775 - 1783
• Main Authors: Ito, Naoki, Hori, Atsushi, Yabe, Takeshi, Nagai, Takayuki, Oikawa, Tetsuro, Yamada, Haruki, Hanawa, Toshihiko
• Format: Journal Article
• Language: English; Japanese
• Published: Japan The Pharmaceutical Society of Japan 01.10.2012; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Animals; antidepressant-like effect; Antidepressive Agents - pharmacology; Antidepressive Agents - therapeutic use; Arginine - analogs & derivatives; Arginine - pharmacology; cell proliferation; Cell Proliferation - drug effects; Depression - drug therapy; Depression - metabolism; Disease Models, Animal; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - metabolism; Intracellular Signaling Peptides and Proteins - blood; kososan; Male; Medicine, Kampo; Mice; neuropeptide Y; Neuropeptide Y - antagonists & inhibitors; Neuropeptide Y - metabolism; Neuropeptides - blood; orexin A; Orexins; Signal Transduction - drug effects; Stress, Psychological - drug therapy; Stress, Psychological - metabolism
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b12-00466

Neuropeptide Y (NPY) and Orexin-A (OX-A), well-known neuropeptides associated with feeding and arousal, show antidepressant-like properties via hippocampal cell proliferation. Previous studies have revealed that kososan, a Kampo (Japanese herbal) medicine, has an antidepressant-like effect in behavioral animal models of depression; the mechanisms underlying this effect may involve the orexinergic system and subsequent upregulation of hippocampal cell proliferation. However, the roles of NPY in kososan's antidepressant-like effect remain unclear. Here we investigated whether the regulation of the NPY system could play crucial roles in this effect in the stress-induced depression-like model mice. The antidepressant-like effect of kososan administered orally (1.0 g/kg) for 28 d was abolished by a continuous intracerebroventricular injection of BIBO3304, a neuropeptide Y1 receptor antagonist, for 7 d. Likewise, BIBO3304 injection blocked the kososan-induced increases in hippocampal cell proliferation and cluster formation of neural progenitor cells. On the other hand, BIBO3304 injection did not affect kososan-induced increases in hypothalamic OX-A-producing cells or in serum OX-A levels. These results suggest that the control of the NPY system in the brain plays an essential role in kososan's antidepressant-like effect and facilitates hippocampal cell proliferation, both of which could be attributed, at least in part, to the control of the NPY system subsequent to the control of the OX-A system.