吗啡诱发条件性位置偏爱激活时大鼠伏隔核前额叶皮层p-CREB、c-Fos的变化

Effect of morphine-reactivated conditioned place preference on p-CREB, c-Fos expression in rat nucleus accumbens and prefrontal cortex

目的探讨吗啡诱发条件性位置偏爱激活时大鼠伏隔核、前额叶皮层磷酸化cAMP反应元件结合蛋白（phospho—cAMP response element binding protein，p-CREB）和c-Fos表达的变化。方法以剂量递增法连续皮下注射（SC）吗啡6d建立大鼠条件性位置偏爱（conditioned place preference，CPP）模型，第7天用生理盐水替代吗啡训练大鼠10d，使形成的CPP逐渐消退，单次SC4mg·kg^-1吗啡激发已消退的CPP。采用免疫组化技术测定吗啡激发CPP重现时大鼠伏隔核、前额叶皮层p-CREB和c-Fos的变化。结果（1）吗啡可使大鼠产生CPP效应，吗啡4mg·kg^-1可使已消失的CPP效应激活；（2）与对照组相比吗啡诱发的CPP激活时大鼠伏隔核、前额叶皮层p-CREB（161．18±5．37，179．75±7．68）和c-Fos（176．63±8．42，185．11±5．61）的表达增加，与NS组比较差异有显著性（P〈0．05）。结论伏隔核、前额叶皮层p-CREB和c-Fos蛋白表达参与了吗啡的CPP重现。

Objective To detect the effect of morphine-reactived conditioned place preference（CPP） on phospho-cAMP response element binding protein （p-CREB） and c-Fos expression in rat nucleus accumbens and prefrontal cortex. Methods Morphine was administered by subcutaneous injection at gradually increasing dose （from 10mg · kg^-1 to 60 mg · kg^-1 ） for 6 days to establish morphine CPP. From day 7,the rats were administered saline instead of morphine for 10 days to induce CPP extinction. The rats were given a single priming injection of morphine 4 mg · kg^- 1 to reactive the morphine CPP. The expression of p-CREB and c-Fos were assayed with immunohistochemistry method in the phase of reoccurrence of CPP. Results （ 1 ） Increasing dose of morphine conditioning for 6 days resulted in acquisition of CPP and morphine （4mg · kg^-1 ） reactivated CPP following 10 days drug free period. （2） Compared to saline control, morphine-reactivated CPP elevated the expression of p-CREB and c-Fos in nucleus accumbens and prefrontal cortex in rats（ P 〈 0.05 ）. Condusion p-CREB and c-Fos expression in nucleus accumbens, prefrontal cortex may be involved in the mechanisms of reoccurrence of CPP.