Responses of hypothalamo–pituitary–adrenal axis to a cholinesterase inhibitor
Responses of hypothalamo–pituitary–adrenal axis to a cholinesterase inhibitor
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DOI：
10.1097/wnr.0b013e3283313eb7
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发表时间：
2009-10
期刊：
影响因子：
1.7
通讯作者：
H. Umegaki;A. Yamamoto;Yusuke Suzuki;A. Iguchi
中科院分区：
文献类型：
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作者：
H. Umegaki;A. Yamamoto;Yusuke Suzuki;A. Iguchi
急性胃肠道事件（主要表现为恶心、呕吐或食欲不振）是所有用于治疗阿尔茨海默病的胆碱酯酶抑制剂的一类效应。然而，其潜在机制尚不清楚。由于促肾上腺皮质激素释放激素与食欲控制有关，我们重点研究了大鼠在服用胆碱酯酶抑制剂多奈哌齐后下丘脑-垂体-肾上腺系统的激活和食物摄入。第一次给药多奈哌齐后3小时和每天给药多奈哌齐后2周，我们监测了室旁核中促肾上腺皮质激素c-Fos的血浆浓度和大鼠饲料摄入量。多奈哌齐灌胃3 mg/kg显著提高了大鼠血浆促肾上腺皮质激素水平和室旁核c-Fos表达，降低了大鼠第一天的进食量。口服该药后促肾上腺皮质激素升高和食欲下降在每日给药2周后减弱。
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.