Effect of agmatine on the development of morphine dependence in rats: potential role of cAMP system.
Effect of agmatine on the development of morphine dependence in rats: potential role of cAMP system.
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DOI：
10.1016/j.ejphar.2004.10.011
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发表时间：
2004-11
影响因子：
5
通讯作者：
F. Aricioglu;Andrea Means;S. Regunathan
中科院分区：
文献类型：
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作者：
F. Aricioglu;Andrea Means;S. Regunathan
胍丁氨酸是一种源自精氨酸的内源性胺，可增强吗啡镇痛作用，并阻断大鼠纳洛酮沉淀的吗啡戒断症状。在本研究中，我们试图确定在吗啡依赖发展过程中使用胍丁胺治疗是否能抑制戒断症状，并且这种作用是由cAMP系统介导的。大鼠暴露于吗啡7天后，出现明显的纳洛酮引起的戒断症状，胍丁胺与吗啡联合治疗可显著减轻戒断症状。与纳洛酮孵育后，吗啡处理的大鼠脑片cAMP水平明显升高，而吗啡和胍丁胺处理的大鼠脑片cAMP水平明显降低。当胍丁氨酸与吗啡同时使用时，吗啡暴露后蓝斑处酪氨酸羟化酶的诱导也减少。我们得出结论，胍丁氨酸减少了对吗啡依赖的发展，这种作用可能是通过慢性吗啡暴露过程中cAMP信号通路的抑制介导的。
Agmatine is an endogenous amine derived from arginine that potentiates morphine analgesia and blocks symptoms of naloxone-precipitated morphine withdrawal in rats. In this study, we sought to determine whether treatment with agmatine during the development of morphine dependence inhibits the withdrawal symptoms and that the effect is mediated by cAMP system. Exposure of rats to morphine for 7 days resulted in marked naloxone-induced withdrawal symptoms and agmatine treatment along with morphine significantly decreasing the withdrawal symptoms. The levels of cAMP were markedly increased in morphine-treated rat brain slices when incubated with naloxone and this increase was significantly reduced in rats treated with morphine and agmatine. The induction of tyrosine hydroxylase after morphine exposure was also reduced in locus coeruleus when agmatine was administered along with morphine. We conclude that agmatine reduces the development of dependence to morphine and that this effect is probably mediated by the inhibition of cAMP signaling pathway during chronic morphine exposure.