孕酮对吗啡条件性位置偏爱大鼠相关脑区中枢多巴胺D2受体水平的影响

目的观察孕酮对于吗啡所致奖赏效应及相关脑区中D2受体水平的影响。方法 32只SD大鼠随机分为空白对照组、吗啡组、孕酮组和孕酮加吗啡组,建立吗啡条件性位置偏爱(CPP)模型,采用免疫组化法测定大鼠伏隔核、腹侧被盖区和纹状体D2受体的水平。结果与空白对照组比较,5mg·kg-1吗啡可诱导大鼠产生稳定的CPP效应(P<0.01),15mg·kg-1孕酮虽自身不能产生CPP效应,但与吗啡合用时能抑制吗啡CPP效应的获得。与空白对照组比较,吗啡组大鼠伏隔核、腹侧被盖区和纹状体中D2受体的平均光密度值降低(均为P<0.01)。与吗啡组比较,合用15mg·kg-1孕酮可使伏隔核和纹状体中D2受体的平均光密度值升高(P<0.01和P<0.05),而在腹侧被盖区中未见变化。结论孕酮可以有效抑制吗啡CPP效应,其机制可能与其逆转吗啡诱导的伏隔核和纹状体中D2受体水平的变化有关。

Effects of progesterone on morphine-induced conditioned place preference and expression levels of D2-receptor in related regions of rat brian

Aim To investigate the effects of progesterone on morphine rewarding effect and levels of D2-receptor in nucleus accumbens,ventral tegmen tal area and striatum.Methods 32 male SD rats were designated to 4 groups randomly with 8 in each,including blank control group,morphine group,progesterone group and progesterone plus morphine group.Conditioned place preference(CPP) test was used to investigate the morphine rewarding effect,and immunohistochemistry was established to determine the levels of D2-receptor in nucleus accumbens,ventral tegmen tal area and striatum.Results Compared with blank control group,5 mg·kg-1 morphine successfully induced the formation of CPP(P<0.01) .15 mg·kg-1 progesterone alone was not able to induce CPP effect,but could abolish the morphine CPP effect.Compared with blank control group,the expression of D2-receptor following morphine administration were decreased in nucleus accumbens,ventral tegmen tal area and striatum(both were P<0.01) .Compared with morphine group,the expression of D2-receptor were increased by co-administration with 15 mg·kg -1 dose of progesterone in striatum and nucleus accumbens(P<0.05 and P<0.01) .Conclusion It is speculated that progesterone could attenuate morphine induced CPP effectively.The effect of progesterone on morphine-induced CPP could be attributed to its action on the changes of D2receptor expression in striatum and nucleus accumbens.