中药AY注射液的主要药效学研究

目的评价中药AY注射液对吗啡依赖性小鼠、大鼠催促戒断的治疗作用.方法用扭体法、热板法致痛考察中药AY注射液镇痛作用,并且以剂量递增方法形成吗啡依赖模型,用纳洛酮催促戒断.结果中药AY注射液无显著镇痛效应,注射液大、中、小剂量(10.8g/kg、5.4g/kg、2.7g/kg)均能减轻小鼠注射纳洛酮后跳跃反应,但只有小剂量组可以减轻小鼠体重下降.结论中药AY注射液能明显抑制大鼠的戒断反应,其中中药AY注射液大、中、小剂量能明显抑制大鼠异常姿势、激惹、咬牙、流泪、腹泻、流涎等症状(评分值P＜0.05～0.001);均能明显抑制大鼠体重下降(P＜0.05～0.01).     

Effects of central application of naloxone on the skin temperature response in morphine-dependent rats

This study was designed to identify if the surge in tail skin temperature (TST) observed following systemic administration of naloxone to morphine-dependent rats is mediated by a specific brain locus. Female rats were fitted with cannula located either in the preoptic area-anterior hypothalamus, locus coeruleus, or the frontal cortex. TST was monitored every 5 min for 60 min following central administration of naloxone (1-40 micrograms/0.4 microliters), in morphine-dependent rats. Regardless of the central site of naloxone injection, TST was significantly increased 4-5 degrees C. A threshold dose of 20 micrograms/0.4 microliters (10 micrograms/0.2 microliters, bilaterally) of naloxone was identified to produce this surge in TST in all three brain regions. These results suggest that morphine dependency sensitizes several brain regions to administration of naloxone such that the narcotic antagonist produces a similar change in TST as is observed following its systemic administration. These data further support the use of our morphine-dependent rat model to study the central mechanisms of the menopausal hot flush, and provide additional evidence that the flush response is centrally mediated.     

扶正口服液对吗啡依赖大鼠血清NO、NOS的影响

目的:观察扶正口服液(以下简称FZY)对吗啡依赖大鼠戒断症状及血清NO和一氧化氮合成酶(NOS)的影响。方法:剂量递增sc吗啡建立14d大鼠吗啡依赖模型,观察FZY对纳洛酮催促大鼠戒断症状的影响,并用分光光度法测定大鼠血清中NO含量和NOS活性。结果:①FZY两个剂量(5.48、10.96g生药/kg)可显著降低吗啡依赖大鼠催促戒断症状分值(P<0.01),且10.96g生药/kg能明显抑制戒断引起的体重下降(P<0.01);②FZY两个剂量(5.48、10.96g生药/kg)可显著降低血清NO含量和NOS活性,效应呈剂量相关性。结论:扶正口服液能缓解吗啡依赖大鼠戒断症状,其机制可能与抑制体内NOS活性,进而下调NO水平有关。     

扶正口服液对吗啡依赖大鼠血清NO、NOS的影响

目的：观察扶正口服液（以下简称FZY）对吗啡依赖大鼠戒断症状及血清NO和一氧化氮合成酶（NOS）的影响。方法：剂量递增sc吗啡建立14d大鼠吗啡依赖模型,观察FZY对纳洛酮催促大鼠戒断症状的影响,并用分光光度法测定大鼠血清中NO含量和NOS活性。结果：①FZY两个剂量（5.48、10.96g生药/kg）可显著降低吗啡依赖大鼠催促戒断症状分值（P〈0.01）,且10.96g生药/kg能明显抑制戒断引起的体重下降（P〈0.01）;②FZY两个剂量（5.48、10.96g生药/kg）可显著降低血清NO含量和NOS活性,效应呈剂量相关性。结论：扶正口服液能缓解吗啡依赖大鼠戒断症状,其机制可能与抑制体内NOS活性,进而下调NO水平有关。     

Dopaminergic—cholinergic interactions in naloxone-induced circling in morphine-dependent rats with nigral lesions

3–4 weeks after placement of a unilateral, electrolytic lesion of the substantia nigra zona compacta, rats were highly dependent on morphine by the s.c. morphine pellet implantation technique. Following challenge with a supramaximal naloxone dose of 20 mg/kg i.p., both continous contralateral circling behavior and severe withdrawal signs in morphine-dependent, lesioned rats were elicited. After various drug pretreatments, the contralateral circling behavior precipitated by naloxone was: (a) reversed to ipsilateral circling by i.p. apomorphine or d-amphetamine, (b) unaltered by i.p. haloperidol or intraneostriatal arecoline administered into the intact neostriatum, and (c) reversed to ipsilateral circling by the administration of atropine into the intact neostriatum. Atropine, apomorphine and amphetamine all interfered with the manifestation of naloxone-precipitated abstinence. These data suggest that a diminution of dopaminergic or an enhancement of cholinergic activities, or both, occur at the level of the neostriatum during naloxone-precipitated withdrawal in morphine-dependent rats.