吗啡成瘾和应激诱导成瘾复发的大鼠脑内神经甾体水平的变化(英文)

Change in brain neurosteroid level of rats in morphine addiction and stress-induced addiction relapse condition

目的观察大鼠吗啡成瘾及应激诱导成瘾复发是否与脑组织神经甾体水平的变化有关。方法给大鼠注射吗啡（5mg·kg^-1·d^-1，ip，18：00～20：00）并在条件性位置偏爱（CPP）箱中训练，每日1次，连续10d，最后1次给药后24h测试大鼠是否产生CPP。再经过7d的自然消退期后，给予足底电击（0．5mA，0．5S，间隔40s，15min）诱发大鼠CPP复发，电击后2h进行CPP测试。测试后立即取样，取样时间18：00～20：00，气相色谱-质谱联用技术测定大鼠脑组织神经甾体。结果给予吗啡并训练10d，大鼠形成明显的CPP，同时脑组织内神经甾体孕烯醇酮和别孕烷醇酮水平显著升高。经过7d的自然消退后再给予足底电击可诱发大鼠CPP复发，脑组织神经甾体脱氧表雄酮和硫酸脱氢表雄酮水平显著升高。结论大鼠吗啡成瘾及应激诱导成瘾复发过程可能与脑组织内源性神经甾体水平有关。

AIM To investigate if morphine addiction and relapse to morphine-seeking is related to the change in neurosteroid levels in the brain of rats. METHODS Rats were injected ip morphine （5 mg· kg^-1·d^-1, 18：00 -20：00） and trained in conditioned place preference （CPP） box, once daily for 10 d. CPP test was performed 24 h after the last training. After discontinuation of training for 7 d for CPP extinction, then intermittent and inescapable foot-shock （FS, 0.5 mA, 0.5 s on, 40 s off, 15 min） was applied to rats as the priming stimuli for relapse. CPP test was performed 2 h after FS. When CPP test finished, rats were decapitated and the levels of neurosteroids were analyzed using gas chromatography/mass spectrometry. RESULTS CPP was established when rats were injected morphine and trained for 10 d. At the same time, the levels of pregnenolone and allopregnanolone in the brain tissues of rats were significantly increased. When CPP was reinstated in morphine-treated rats by FS-stress after 7 d CPP extinction, the levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate were significantly increased. CONCLUSION The development of morphine addiction and relapse may be related to endogenous neurosteroids in rat brain tissues.