三氟拉嗪抑制吗啡依赖大、小鼠纳洛酮催促的戒断症状

目的　研究三氟拉嗪对吗啡依赖大、小鼠纳洛酮催促戒断症状的影响 ,并探讨其机制。方法　吗啡依赖大、小鼠纳洛酮催促实验。结果　三氟拉嗪 (2～ 2 0mg·kg-1)呈剂量依赖性抑制吗啡依赖小鼠纳洛酮催促所致的跳跃、湿狗样抖动、前爪震颤和体重下降。三氟拉嗪 5～ 2 0mg·kg-1ip ,对吗啡依赖大鼠大部分纳洛酮催促的阳性戒断症状均具有明显的抑制作用 ,其中包括跳跃、湿狗样抖动、排泄物、体重下降、咬牙、流涎、腹泻、上睑下垂、激惹。作为DA1/DA2 受体激动剂 ,阿朴吗啡 (2～ 8mg·kg-1)对三氟拉嗪抑制吗啡依赖小鼠纳洛酮催促戒断症状无明显影响 ,而钙通道阻滞剂硝苯吡啶 (5～ 2 0mg·kg-1)则呈剂量依赖性加强三氟拉嗪对吗啡依赖小鼠纳洛酮催促戒断症状的抑制作用。结论　三氟拉嗪对吗啡依赖大、小鼠纳洛酮催促的戒断症状具有明显的抑制作用。对受体后钙调素生物活性的抑制作用可能是三氟拉嗪抗吗啡依赖大、小鼠躯体戒断症状主要机制 ,而中枢神经系统DA2 受体可能不参与三氟拉嗪对吗啡躯体戒断症状的抑制作用

Trifluoperazine attenuates naloxone-precipitated symptoms in morphine-dependent rats and mice

AIM To investigate the effects of trifluoperazine on naloxone precipitated withdrawal symptoms in morphine dependent rats and mice, and its pharmacological mechanisms. METHODS\ Naloxone precipitated tests in morphine dependent rats and mice were used. RESULTS\ Trifluoperazine(2～20 mg·kg -1 ) dose dependently inhibited naloxone precipitated withdrawal jumping, wet dog shakes, paw tremor and weight loss in morphine dependent mice. With ip trifluoperazine (5～20 mg·kg -1 ), most of positive withdrawal symptoms, including jumping, wet dog shakes, defeacation, weight loss, teeth chattering, salivation, diarrhea, ptosis and irritating, induced by naloxone in morphine dependent rats were significantly reduced. Apomorphine (2～8 mg·kg -1 ), a mixed DA 1/DA 2 receptor agonist, did not affect inhibition of trifluoperazine on naloxone precipitated withdrawal symptoms in morphine dependent mice. However, nifedipine(5～20 mg·kg -1 ), a L type voltage sensitive calcium channel blocker, enhanced a pharmacological action of trifluoperazine against naloxone precipitated symptoms in morphine dependent mice. CONCLUSION\ Trifluoperazine attenuates naloxone precipitated withdrawal symptoms in morphine dependent rats and mice by inhibiting the activity of post receptor calmodulin, but it does not antagonizes DA 2 receptor, in central nervous system.