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首页> 外文期刊>Addiction biology >Orexin A-mediated AKT signaling in the dentate gyrus contributes to the acquisition, expression and reinstatement of morphine-induced conditioned place preference
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Orexin A-mediated AKT signaling in the dentate gyrus contributes to the acquisition, expression and reinstatement of morphine-induced conditioned place preference

机译：齿状回中Orexin A介导的AKT信号传导促进吗啡诱导的条件性位置偏爱的获得，表达和恢复

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摘要

Accumulating evidence indicates that the hippocampal dentate gyrus (DG), a critical brain region contributing to learning and memory, is involved in the addiction and relapse to abused drugs. Emerging studies also suggest the role of orexin signaling in the rewarding behavior induced by repeated exposure to opiates. In the present study, we investigated the dynamic adaptation of orexin signaling in the DG and its functional significance in the acquisition, expression, maintenance of and relapse to rewarding behavior induced by morphine. Repeated place conditioning with morphine significantly increased the orexin A content released from the lateral hypothalamic area projecting neurons into the DG. Local infusions of orexin A into the DG sensitized the acquisition of and relapse to the conditioned place preference induced by morphine. The application of the orexin receptor type 1 (OXR1) antagonist SB334867 significantly abolished the acquisition, expression and maintenance of the conditioned place preference induced by repeated exposure to morphine. Furthermore, the significant increase of the phosphorylation of AKT in the DG was associated with preference for the morphine-paired chamber in rats, which was reversed by the local administration of an OXR1 antagonist. Thus, these findings suggested that the dynamic upregulation of orexin A signaling, via the AKT pathway in the DG, may promote the acquisition and maintenance of opioid-induced craving behaviors and may increase sensitivity to the rewarding effect of subsequent opioids.
机译：越来越多的证据表明，海马齿状回（DG）是有助于学习和记忆的重要大脑区域，与成瘾和滥用药物的复发有关。新兴研究还表明，食欲肽信号传导在反复接触阿片引起的奖励行为中的作用。在本研究中，我们研究了食欲素信号在DG中的动态适应及其在吗啡诱导的奖励行为的获取，表达，维持和复发中的功能意义。用吗啡反复进行位置调节可显着增加从下丘脑外侧区域释放的食欲素A含量，从而将神经元投射到DG中。向DG中局部注入orexin A使由吗啡引起的条件性位置偏爱的获得和复发。 Orexin受体1型（OXR1）拮抗剂SB334867的应用显着取消了重复暴露于吗啡引起的条件位置偏爱的获得，表达和维持。此外，DG中AKT磷酸化的显着增加与大鼠对吗啡配对腔的偏爱有关，这可通过局部施用OXR1拮抗剂来逆转。因此，这些发现表明，通过DG中的AKT途径，食欲蛋白A信号传导的动态上调可能促进阿片样物质诱导的渴望行为的获得和维持，并且可能增加对后续阿片样物质的奖励作用的敏感性。

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