NEUROENDOCRINOLOGYResponses of hypothalamo–pituitary–adrenal axis to a cholinesterase inhibitorUmegaki, Hiroyuki; Yamamoto, Aki; Suzuki, Yusuke; Iguchi, AkihisaAuthor Information Department of Geriatrics, Nagoya University Graduate School of Medicine, Tsuruma-Cho, Showa-Ku, Nagoya, Aichi, Japan Correspondence to Dr Hiroyuki Umegaki, Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsuruma-Cho, Showa-Ku, Nagoya, Aichi 466-8550, Japan Tel: +81 52 744 2365; fax: +81 52 744 2371; e-mail: email@example.com Received 8 July 2009 accepted 23 July 2009 NeuroReport: October 7th, 2009 - Volume 20 - Issue 15 - p 1366-1370 doi: 10.1097/WNR.0b013e3283313eb7 Buy SDC Metrics Abstract Acute gastrointestinal events (mostly manifested by nausea, vomiting, or loss of appetite) are class effects of all cholinesterase inhibitors, which are prescribed for the treatment of Alzheimer's disease. The underlying mechanism, however, has been unclear. Because corticotropin-releasing hormone is related to appetite control, we focused on the activation of the hypothalamo–pituitary–adrenal system and food intake following the administration of the cholinesterase inhibitor, donepezil, in rats. We monitored the plasma concentrations of adrenocorticotropic hormone, c-Fos, in the paraventricular nucleus, and intakes of rat chow for 3 h after the first administration of donepezil, and 2 weeks later, after daily administration of donepezil. The intragastric administration of 3 mg/kg of donepezil significantly increased the plasma adrenocorticotropic hormone levels and c-Fos expression in the paraventricular nucleus, and decreased the food intake on the first day. The increase in adrenocorticotropic hormone and loss of appetite after oral administration of the drug were attenuated after daily administration for 2 weeks. © 2009 Lippincott Williams & Wilkins, Inc.