Role of 5-HT1A receptor-mediated serotonergic transmission in the medial prefrontal cortex in acute restraint stress-induced augmentation of rewarding memory of cocaine in mice
Role of 5-HT1A receptor-mediated serotonergic transmission in the medial prefrontal cortex in acute restraint stress-induced augmentation of rewarding memory of cocaine in mice
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DOI：
10.1016/j.neulet.2020.135555
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发表时间：
2021-01-19
影响因子：
2.5
通讯作者：
Kaneda，Katsuyuki
中科院分区：
文献类型：
--
作者：
Chu，Jinling;Deyama，Satoshi;Kaneda，Katsuyuki
压力会增强对可卡因的渴望。我们最近报道了急性束缚应激增加小鼠可卡因条件性位置偏爱（CPP），然而，其潜在机制尚不清楚。本研究旨在研究急性束缚应激引起内侧前额叶皮层（mPFC）细胞外5-羟色胺（5-HT）水平升高，从而在可卡因CPP增强中，内侧前额叶皮层（mPFC）中的多巴胺能传递的作用。在非应激条件下，在测试前mPFC内输注选择性5-羟色胺再摄取抑制剂（S）-西酞普兰显著增加了可卡因CPP评分。这表明增加的mPFC 5-HT水平在可卡因CPP增强中的实质性作用。此外，内mPFC和系统管理的5-HT 1A受体拮抗剂WAY 100635之前立即约束应激暴露显着衰减应激诱导的可卡因CPP增强。我们的研究结果表明，通过mPFC中的5-HT 1A受体增强的可卡因能传递参与了急性应激诱导的可卡因奖赏记忆增强;此外，5-HT 1A受体可能是应激诱导的可卡因渴望的治疗靶点。
Stress enhances cocaine craving. We recently reported that acute restraint stress increases cocaine conditioned place preference (CPP) in mice; however, the underlying mechanisms remain unclear. This study aimed to examine the role of serotonergic transmission in the medial prefrontal cortex (mPFC) in cocaine CPP enhancement by acute restraint stress, which increases extracellular serotonin (5-HT) levels in the mPFC. Intra-mPFC infusion of the selective serotonin reuptake inhibitor (S)-citalopram prior to the test session significantly increased the cocaine CPP score under non-stressed conditions. This is indicative of the substantial role of increased mPFC 5-HT levels in cocaine CPP enhancement. Moreover, intra-mPFC and systemic administration of the 5-HT1Areceptor antagonist WAY100635 immediately before restraint stress exposure significantly attenuated stress-induced cocaine CPP enhancement. Our findings suggest that enhanced serotonergic transmission via 5-HT1Areceptors in the mPFC is involved in acute stress-induced augmentation of rewarding memory of cocaine; moreover, the 5-HT1Areceptor could be a therapeutic target for stress-induced cocaine craving.