INHIBITION OF HEAD TWITCH RESPONSE TO QUIPAZINE IN RATS BY CHRONIC AMITRIPTYLINE BUT NOT FLUVOXAMINE OR CITALOPRAM
INHIBITION OF HEAD TWITCH RESPONSE TO QUIPAZINE IN RATS BY CHRONIC AMITRIPTYLINE BUT NOT FLUVOXAMINE OR CITALOPRAM
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DOI：
10.1007/bf00180825
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发表时间：
1986-01-01
影响因子：
3.4
通讯作者：
MELZACKA, M
中科院分区：
文献类型：
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作者：
PAWLOWSKI, L;MELZACKA, M
慢性（每天两次/14天），但不是急性的，10 mg/kg PO阿米替林治疗减少了大鼠中喹嗪（5 mg/kg）引起的头部抽搐的次数，在最后一次给药后2小时（但不是72小时）测量。使用氟伏沙明或西酞普兰进行类似治疗，它们是比阿米替林更有效且特异性更高的血清素摄取抑制剂，但不会影响奎帕嗪诱导的反应。在急性实验中，氟伏沙明 (10 mg/kg PO) 和西酞普兰 (10 mg/kg PO) 增强了 L-5-羟色氨酸 (50 mg/kg IP) 与外周脱羧抑制剂 Ro 4-4602 (25 mg/kg IP) 诱导的头部抽搐反应。阿米替林（10 mg/kg PO）略微减少 L-5-羟色氨酸（5-HTP）引起的头部抽搐的次数。较高剂量的阿米替林（20-40 mg/kg PO）也抑制了喹嗪引起的头部抽搐反应。在最后一次口服10 mg/kg慢性剂量后0.5-24测得的阿米替林脑水平总是远高于急性口服20或40 mg/kg剂量后相同时间间隔观察到的水平。获得的结果表明，在阿米替林长期治疗过程中，突触后而不是突触前机制导致中枢血清素受体不敏感的发展。
Chronic (twice daily/14 days), but not acute, treatment with 10 mg/kg PO amitriptyline reduced the number of quipazine (5 mg/kg)-induced head twitches in rats, measured 2 h (but not 72 h) after the last administration of the drug. Similar treatment with fluvoxamine or citalopram, which are more potent and much more specific serotonin uptake inhibitors than amitriptyline, did not affect the quipazine-induced response. In acute experiments, fluvoxamine (10 mg/kg PO) and citalopram (10 mg/kg PO) potentiated the head twitch reaction induced by L-5-hydroxytryptophan (50 mg/kg IP) given together with Ro 4-4602 (25 mg/kg IP), a peripheral decarboxylate inhibitor. Amitriptyline (10 mg/kg PO) slightly decreased the number of L-5-hydroxytryptophan (5-HTP)-induced head twitches. Higher doses of amitriptyline (20-40 mg/kg PO) also inhibited the quipazine-induced head twitch reaction. The brain level of amitriptyline measured 0.5-24 after the last oral administration of the chronic dose of 10 mg/kg was always much higher than that observed at the same time intervals after an acute oral dose of 20 or 40 mg/kg. The results obtained indicate that a postsynaptic rather then presynaptic mechanism is responsible for the development of subsensitivity of the central serotonin receptors in the course of chronic treatment with amitriptyline.