慢性吗啡耐受大鼠脑内孤啡肽生成与释放增加

INCREASED RELEASE OF ORPHANIN FQ (OFQ) IN BRAIN OF CHRONIC MORPHINE TOLERANT RATS

本文采用放射免疫分析法测定了慢性吗啡耐受过程中大鼠脑室灌流液、中脑导水管周围灰质（ＰＡＧ） 及杏仁核中孤啡肽（ＯＦＱ） 免疫活性（ｉｒ） 的动态变化。结果观察到：（１） 大鼠连续５ ｄ 皮下注射递增剂量的盐酸吗啡造成慢性吗啡耐受， 其脑室灌流液中ＯＦＱｉｒ 随吗啡注射剂量和注射次数的增加逐渐上升， 第５ ｄ 注射后较对照组升高了５２ ％ （ Ｐ＜ ０－０１） ；（２） 皮下注射吗啡１ ｄ （１０ ｍｇ／ｋｇ，ｔｉｄ） 、３ ｄ （４０ ｍｇ／ｋｇ，ｔｉｄ） 、５ ｄ （６０ ｍｇ／ｋｇ，ｔｉｄ） 的大鼠ＰＡＧ中ＯＦＱｉｒ 比对照组分别升高了１７ ％ （ Ｐ＜ ０－０５） 、４８ ％ （ Ｐ＜ ０－０５） 和８０ ％ （ Ｐ＜ ０－０１） ；（３） 杏仁核中ＯＦＱｉｒ 在吗啡注射３ 、５ ｄ 后较对照组分别升高了３６ ％ （ Ｐ＜ ０－０５） 和５５ ％ （ Ｐ＜ ０－０５） 。结果提示： 长时间大剂量给予外源性吗啡可加速脑内ＯＦＱ的生成和释放， 这可能是慢性吗啡耐受形成机制之一。

The changes in OFQ immunoreactivity (OFQ ir) content and release of cerebro^ventricular perfusate, periaqueductal gray (PAG) and amygadala of chronic morphine tolerant rats were measured with radioimmunoassay (RIA). The results indicate: (1) chronic morphine tolerance was achieved in rats by injecting increasing doses of morphine (10, 20, 40, 50, 60 mg/kg, sc, tid). The content of OFQ ir in cerebroventricular perfusate in the rats of normal saline (NS) group remained at a steady level during the injections from d 1 to d 5, while in the morphine treated group of rats the content of OFQ ir showed 25% increase ( P <0 05 vs NS) and 52% increase ( P <0 01 vs NS) after 3 and 5 days′ morphine injection respectively. (2) The content of OFQ ir in PAG of rats receiving morphine injection for 1, 3 and 5 days showed respectively increases of 17% ( P <0 05), 48% ( P <0 05) and 80% ( P <0 01) against the NS group. (3) The content of OFQ ir in rat amygdala receiving 1 day injection of morphine showed a 8% decrease, which was not significantly different from NS group. However, there was a 36% and 55% ( P <0 05) increase respectively after injection for 3 and 5 days. It is suggested that in the later stage of chronic morphine treatment, large amount of OFQ was released from rat brain to antagonize the effect of opioids, which may play an important role in the development of morphine tolerance.