San-Martin-Clark O, Leza J C, Lizasoain I, Lorenzo P
Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
Psychopharmacology (Berl). 1993;111(2):233-8. doi: 10.1007/BF02245529.
This study was designed to explain the action of sodium cromoglycate (CRO) on the brain serotonergic system in control, morphine tolerant (by SC implantation of a 75 mg morphine pellet), and also in morphine dependent mice just before naloxone-precipitated withdrawal. After SC injections of CRO in control mice, morphine tolerant mice (day 4 of addiction), and 1 h before abstinence (withdrawal was induced by SC injection of 1 mg/kg naloxone on day 4 of addiction), animals were decapitated and various brain areas were rapidly removed. 5HT (Serotonin) and 5HIAA (5-hydroxyindole-3-acetic acid) were measured by high performance liquid chromatography coupled with electrochemical detection (HPLC-ECD). The ratio 5HIAA/5HT provided one index by which the turnover of the indoleamine was measured. CRO increased the turnover of 5HT in most of the brain areas studied in both control and morphine dependent mice. Furthermore, previous administration of CRO prior to naloxone challenge induced a significant increase in the 5HIAA/5HT ratio in the hypothalamus and striatum. These results are discussed as the reason for the preventive effect of CRO on jumping behaviour in morphine abstinent mice.
本研究旨在解释色甘酸钠（CRO）对正常小鼠、吗啡耐受小鼠（通过皮下植入75mg吗啡微丸形成）以及在纳洛酮诱发戒断前的吗啡依赖小鼠脑内5-羟色胺能系统的作用。在正常小鼠、吗啡耐受小鼠（成瘾第4天）皮下注射CRO后，以及在成瘾第4天通过皮下注射1mg/kg纳洛酮诱发戒断前1小时，将动物断头并迅速取出各个脑区。采用高效液相色谱-电化学检测法（HPLC-ECD）测定5-羟色胺（5HT）和5-羟吲哚乙酸（5HIAA）。5HIAA/5HT比值是衡量吲哚胺代谢周转率的一个指标。在正常小鼠和吗啡依赖小鼠的大多数研究脑区中，CRO均增加了5HT的代谢周转率。此外，在纳洛酮激发前预先给予CRO可使下丘脑和纹状体中的5HIAA/5HT比值显著升高。这些结果被作为CRO对吗啡戒断小鼠跳跃行为具有预防作用的原因进行了讨论。
