Leza J C, Lizasoain I, Martín-Clark O S, Lorenzo P
Departamento de Farmacología, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
Psychopharmacology (Berl). 1992;107(4):595-600. doi: 10.1007/BF02245276.
The role of sodium cromoglycate (CRO) on analgesia, locomotor activity and morphine withdrawal in mice was studied in morphine-dependent and drug-naive mice. CRO (0.5, 1, 5, 10, 30, 50 and 100 mg/kg, SC) induces analgesia (hot plate), an effect blocked by previous administration of the opiate antagonist naloxone (1 mg/kg). Furthermore, CRO (30 mg/kg) potentiates morphine analgesia. In morphine-tolerant mice, moderate doses of CRO (0.5, 1, 5, 10 and 30 mg/kg) do not induce analgesia, which suggested the development of cross tolerance between CRO and morphine, whereas coadministration of CRO and morphine in morphine tolerant animals restored the sensitivity to morphine. Administration of CRO (10 and 30 mg/kg) induces an increase in spontaneous locomotor activity, and previous administration of naloxone (1 mg/kg) blocks this effect, whereas CRO (10 mg/kg) blocks morphine (10 mg/kg) and amphetamine (3 mg/kg)-induced hyperactivity. CRO (10, 50 and 100 mg/kg) induces a significant and dose-dependent reduction in the number of jumps ("jumping up") during naloxone (1 mg/kg)-induced withdrawal in morphine-dependent mice. Finally, CRO (100 mg/kg) reduces the "wet dog shake" phenomenom during naloxone-induced withdrawal in morphine-dependent mice. These results suggest a possible stabilizing effect of CRO on the membranes of neurones that mediate analgesia, locomotor activity and opiate abstinence. Changes and inhibition of DA, NA and 5-HT release may also explain these effects.
在吗啡依赖和未接触过药物的小鼠中研究了色甘酸钠（CRO）对小鼠镇痛、运动活性及吗啡戒断反应的作用。CRO（0.5、1、5、10、30、50和100毫克/千克，皮下注射）可诱导镇痛（热板法），该效应可被预先给予的阿片拮抗剂纳洛酮（1毫克/千克）阻断。此外，CRO（30毫克/千克）可增强吗啡的镇痛作用。在吗啡耐受的小鼠中，中等剂量的CRO（0.5、1、5、10和30毫克/千克）不会诱导镇痛，这表明CRO与吗啡之间产生了交叉耐受性，而在吗啡耐受的动物中同时给予CRO和吗啡可恢复对吗啡的敏感性。给予CRO（10和30毫克/千克）可诱导自发运动活性增加，预先给予纳洛酮（1毫克/千克）可阻断此效应，而CRO（10毫克/千克）可阻断吗啡（10毫克/千克）和苯丙胺（3毫克/千克）诱导的多动。CRO（10、50和100毫克/千克）可使吗啡依赖小鼠在纳洛酮（1毫克/千克）诱导的戒断过程中跳跃次数（“向上跳跃”）显著且呈剂量依赖性减少。最后，CRO（100毫克/千克）可减少吗啡依赖小鼠在纳洛酮诱导的戒断过程中的“湿狗样抖动”现象。这些结果提示CRO可能对介导镇痛、运动活性及阿片类药物戒断的神经元膜具有稳定作用。多巴胺、去甲肾上腺素和5-羟色胺释放的变化及抑制也可能解释这些效应。
