Responses of hypothalamo-pituitary-adrenal axis to a cholinesterase inhibitor.
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.
Umegaki
Hiroyuki
H
Department of Geriatrics, Nagoya University Graduate School of Medicine, Tsuruma-Cho, Showa-Ku, Aichi, Japan. umegaki@med.nagoya-u.ac.jp <umegaki@med.nagoya-u.ac.jp>
Yamamoto
Aki
A
Suzuki
Yusuke
Y
Iguchi
Akihisa
A
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D001066:Appetite / Q000187:drug effects / Q000502:physiology; D001069:Appetite Regulation / Q000187:drug effects / Q000502:physiology; D002800:Cholinesterase Inhibitors / Q000009:adverse effects* / Q000633:toxicity*; D000077265:Donepezil; D004334:Drug Administration Schedule; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007189:Indans / Q000494:pharmacology; D008297:Male; D009490:Neurosecretory Systems / Q000187:drug effects* / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D016760:Proto-Oncogene Proteins c-fos; D000077265:Donepezil; D000324:Adrenocorticotropic Hormone