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目的:观察孕酮对于吗啡所致奖赏效应及相关脑区中亮氨酸脑啡肽水平的影响。方法:将40只SD大鼠随机均分为对照组(环糊精)、吗啡组、孕酮组和孕酮+吗啡组,建立吗啡条件性位置偏爱(CPP)模型,上午各组皮下给予相应药物后放入白室训练45min;下午各组均皮下和腹腔给予等量的环糊精和生理盐水后放入黑室训练。连续训练10d后进行CPP测试并处死大鼠取脑组织采用放射免疫法测定大鼠不同脑区中亮氨酸脑啡肽(L-EK)的含量。结果:与对照组比较,吗啡组发生CPP效应,下丘脑、伏隔核和额叶皮质中的L-EK水平显著降低(P<0.05或P<0.01);与吗啡组比较,孕酮+吗啡组CPP效应受到抑制,上述位置中L-EK水平显著升高(P<0.05或P<0.01),而海马和中脑内L-EK水平未见显著性变化。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相关脑区中的L-EK水平的变化有关。
OBJECTIVE: To observe the effect of progesterone on the reward effect induced by morphine and the leucine enkephalin level in the brain regions. Methods: Forty SD rats were randomly divided into control group (cyclodextrin), morphine group, progesterone group and progesterone + morphine group. Morphine-conditioned place preference (CPP) model was established. In the morning, After the drug into the white room training 45min; afternoon, each group were subcutaneously and intraperitoneally administered the same amount of cyclodextrin and saline into the black box training. The CPP test was conducted 10 days after the continuous training and the brain tissues of the rats were sacrificed. The contents of leucine enkephalin (L-EK) in different brain regions of rats were determined by radioimmunoassay. RESULTS: Compared with the control group, the CPP effect was found in morphine group, and the L-EK level in hypothalamus, nucleus accumbens nucleus and frontal lobe cortex decreased significantly (P <0.05 or P <0.01). Compared with morphine group, The CPP effect was inhibited. The levels of L-EK in these sites were significantly increased (P <0.05 or P <0.01), while there was no significant change in L-EK level in hippocampus and midbrain. CONCLUSION: Progesterone can effectively inhibit the CPP effect of morphine, and its mechanism may be related to reversing the change of L-EK level in brain regions induced by morphine.