Glucocorticoid Is Involved in Food-Entrainable Rhythm of μ-Opioid Receptor Expression in Mouse Brainstem and Analgesic Effect of Morphine

Journal of Pharmacological Sciences

Ayaka Matsuo²  Hiroyuki Kiyofuji³  Miyako Yoshida³  Hideto To²  Shigehiro Ohdo¹  Toshihiro Fujioka³  Satoru Koyanagi¹  Shun Higuchi² 

[1] Pharmaceutics, Division of Clinical Pharmacy, Department of Medico-Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Kyushu University, Japan;Clinical Pharmacokinetics, Division of Clinical Pharmacy, Department of Medico-Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Kyushu University, Japan;Department of Instrumental Analysis, Faculty of Pharmaceutical Science, Fukuoka University, Japan

关键词: food-entainale rhythm;    feeding schedule;    glucocorticoid;    μ-opioid receptor;    morphine;   

DOI  :  10.1254/jphs.FP0051075

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(33)Cited-By(4)The repeated manipulation of feeding schedule has a marked influence on the chronopharmaological aspects of many drugs. In this study, we investigated the role of endogenous glucocorticoid in the mechanism by which restricting the feeding time modulates the analgesic effect of morphine. Male ICR mice were housed under a light-dark cycle (light on from 07:00 to 19:00) with food and water ad libitum or under repeated time-restricted feeding (feeding time from 09:00 to 17:00) for 2 weeks before the experiment. Under the ad libitum feeding, mRNA levels of μ-opioid receptor and its binding capacity in mouse brainstem increased around the early dark phase, following the 24-h variation in circulating glucocorticoid levels. As a consequence, potent analgesic effects of morphine were observed in mice injected with the drug during the dark phase. Daily restricted feeding modulated the time-dependency of μ-opioid receptor function, accompanied by the alteration of the rhythm in circulating glucocorticoid levels. Under the time-restricted feeding, potent analgesic effects of morphine were found in mice injected with the drug during the light phase. Because the manipulation of feeding schedule was unable to produce the food-entrainable rhythm in the expression of μ-opioid receptor in the brainstem of adrenalectomized mice, endogenous rhythm of glucocorticoid secretion seems to be involved in the mechanism by which the time-restricted feeding modulates the analgesic effects of morphine.

【 授权许可】

Unknown