Background: The 5-hydroxytryptamine (5-HT) neurotransmitter system and lateral habenula (LHb) are involved in the regulation of depression, while the mechanisms remain to be clarified. Objectives: The effects and possible mecha-nism underlying activation or blockade of 5-HT₄ receptors (5-HT₄Rs) in the LHb in depression were investigated by behavioral and neurochemical methods based on a Parkinson’s disease (PD) rat model. Method: 6-Hydroxydopamine (6-OHDA) was injected unilaterally into the substantia nigra pars compacta to establish the PD rat model. The depressive-like behaviors were measured by the forced swimming test (FST) and sucrose preference test (SPT). The concentrations of dopamine (DA), noradrenaline (NA) and 5-HT in the related brain regions were measured by a neurochemical method. Results: The 6-OHDA lesions increased the immobility time in the FST and decreased the sucrose consumption in the SPT, suggesting the induction of depressive-like behaviors. Intra-LHb injection of BIMU-8 (5-HT₄R agonist) or GR113808 (5-HT₄R antagonist) produced antidepressant effects in the lesioned rats. Intra-LHb injection of BIMU-8 significantly increased the DA levels in the medial prefrontal cortex (mPFC) and ventral hippocampus (vHip), increased the 5-HT level in the mPFC and decreased the NA level in the vHip only in the lesioned rats, while intra-LHb injection of GR113808 changed DA, NA and 5-HT levels in the mPFC, LHb and vHip in both sham and the lesioned rats. Conclusions: All these results suggest that activation or blockade of the LHb 5-HT₄Rs produce antidepressant effects in the 6-OHDA-lesioned rats, which are related to the changes of monoamines in the limbic and limbic-related regions.
Neuropsychobiology

中文翻译：

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外侧缰核中 Serotonin-4 受体的激活和阻断在偏帕金森病大鼠中产生抗抑郁作用。

背景： 5-羟色胺（5-HT）神经递质系统和外侧缰核（LHb）参与抑郁症的调节，但其机制仍有待阐明。目的：通过基于帕金森病 (PD) 大鼠模型的行为和神经化学方法研究抑郁症患者 LHb 中5-HT ₄受体 (5-HT ₄ Rs)激活或阻断的影响和可能机制。方法：将6-羟基多巴胺（6-OHDA）单侧注入黑质致密部，建立PD大鼠模型。通过强迫游泳测试（FST）和蔗糖偏好测试（SPT）测量抑郁样行为。通过神经化学方法测量相关脑区中多巴胺(DA)、去甲肾上腺素(NA)和5-HT的浓度。结果： 6-OHDA 损伤增加了 FST 中的不动时间并减少了 SPT 中的蔗糖消耗，表明诱导了抑郁样行为。LHb 内注射 BIMU-8（5-HT ₄ R 激动剂）或 GR113808（5-HT ₄R 拮抗剂）在受损大鼠中产生抗抑郁作用。LHb 内注射 BIMU-8 显着增加了内侧前额叶皮层 (mPFC) 和腹侧海马 (vHip) 中的 DA 水平，增加了 mPFC 中的 5-HT 水平并降低了仅在损伤大鼠中 vHip 中的 NA 水平，而 LHb 内注射 GR113808 改变了假手术和损伤大鼠的 mPFC、LHb 和 vHip 中的 DA、NA 和 5-HT 水平。结论：所有这些结果表明，LHb 5-HT ₄ Rs 的激活或阻断在 6-OHDA 损伤的大鼠中产生抗抑郁作用，这与边缘和边缘相关区域中单胺的变化有关。
神经心理生物学