修治附子在吗啡诱导的大鼠条件性位置偏爱上的作用

Effects of processed Aconiti tuber on morphine-induced conditioned place preference in rats

目的:探讨修治附子(PAT)在吗啡诱导的大鼠条件性位置偏爱(CPP)模型上的作用及其机制。方法:(1)40只SD大鼠分为5组(n=8):生理盐水组、吗啡组、吗啡+PAT处理1、2和3组。除生理盐水组外,其余4组连续8 d隔天交替皮下注射吗啡5 mg/kg或生理盐水建立CPP模型,并同时每日分别以蒸馏水或PAT(0.3或1.0或3.0g/kg)灌胃。(2)其余32只SD大鼠分为4组(n=8):吗啡组、nor-BNI(kappa受体拮抗剂)+吗啡组、吗啡+PAT组和nor-BNI+吗啡+PAT组。4组大鼠均采用上述方法建立CPP模型。各组大鼠均于吗啡注射前120m in皮下注射生理盐水或nor-BNI(5 mg/kg),PAT处理组每日PAT 3.0 g/kg灌胃,其余2组以蒸馏水灌胃。各组大鼠均于CPP训练前和训练后测定CPP值,训练后测定CPP值后取大鼠脑伏隔核并采用放射免疫法检测其所含强啡肽浓度。结果:(1)经CPP训练后,吗啡诱导引起了CPP值升高。(2)1.0或3.0 g/kg的PAT剂量相关地降低了吗啡诱导引起的CPP升高(P<0.05)。(3)nor-BNI完全拮抗了PAT(3.0 g/kg)对吗啡CPP形成的抑制(P<0.05)。(4)PAT处理组大鼠脑伏隔核强啡肽的浓度比吗啡对照组高(P<0.05),也呈剂量相关。结论:PAT剂量相关地抑制吗啡诱导的CPP形成,具有抗成瘾作用,其抗成瘾作用可能与大鼠脑伏隔核强啡肽的浓度增加,从而激动kappa受体有关。

AIM： To investigate the effect of processed Aconiti tuber（PAT） on morphine-induced conditioned place preference（CPP） in rats.METHODS： Forty rats were randomly divided into 5 groups（n=8）： saline group,morphine group,and morphine plus PAT 1,PAT 2 and PAT 3 groups.The rats in the latter 4 groups were subcutaneously injected with morphine（5 mg/kg） or saline alternately for 8 days and orally administrated with water or PAT at the dose of 0.3,1.0 or 3.0 g/kg once daily.Other 32 rats were also randomly divided into 4 groups： morphine group,morphine ＋ nor-binaltorphimine（nor-BNI,a kappa receptor antagonist） group,morphine ＋ PAT group and morphine ＋ PAT ＋ nor-BNI group.The CPP model was established.The rats were subcutaneously injected with nor-BNI（5 mg/kg） or saline 120 min before morphine was given.Oral PAT（3.0 g/kg） was administrated to PAT-treated rats and oral water was administrated to the other 2 groups once daily.CPP was measured on the day before CPP training and on the 9th day after CPP training.After the last CPP measurement,the nuclei accumbens（NAc） of the rats were obtained and the dynorphin concentration in NAc was measured by radioimmunoassay.RESULTS： Morphine induced the increase in CPP scores of the rats after 8-day CPP training.PAT at 1.0 or 3.0 g/kg dose-dependently reduced morphine-induced increase in CPP scores.Nor-BNI completely antagonized the inhibitory effect of PAT（3.0 g/kg） on morphine-induced CPP.PAT dose-dependently increased dynorphin content in rat NAc after CPP training.CONCLUSION： PAT dose-dependently inhibits morphine-induced CPP in rats.This inhibitory effect is probably mediated by activation of kappa opioid receptors through increasing dynorphin content in rat NAc.