Antidepressant-like Effect of the Eburnamine-Type Molecule Vindeburnol in Rat and Mouse Models of Ultrasound-Induced Depression,ACS Chemical Neuroscience

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Antidepressant-like Effect of the Eburnamine-Type Molecule Vindeburnol in Rat and Mouse Models of Ultrasound-Induced Depression
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2024-01-12 , DOI: 10.1021/acschemneuro.3c00590
Eugene Zubkov _{1,

2} , Olga Riabova ₁ , Yana Zorkina _{1,

2} , Anna Egorova ₁ , Valeriya Ushakova _{1,

2} , Alexander Lepioshkin ₁ , Elena Novoselova ₁ , Olga Abramova _{1,

2} , Anna Morozova ₂ , Vladimir Chekhonin ₂ , Vadim Makarov ₁

Affiliation

Vindeburnol (VIND, RU24722, BC19), a synthetic molecule derived from the eburnamine-vincamine alkaloid group, has many neuropsychopharmacological effects, but its antidepressant-like effects are poorly understood and have only been described in a few patents. To reliably estimate this effect, vindeburnol was studied in a model of long-term variable-frequency ultrasound (US) exposure at 20–45 kHz in male Wistar rats and BALB/c mice. Vindeburnol was administered chronically for 21 days against a background of simultaneous ultrasound exposure at a dose of 20 mg/kg intraperitoneally (IP). Using four behavioral tests, the sucrose preference test (SPT), the social interaction test (SIT), the open field test (OFT), and the forced swimming test (FST), we found that the treatment with the compound diminished depression-like symptoms in mice and rats. The compound restored the ultrasound-related reduced sucrose consumption to control levels and increased social interaction time in mice and rats compared with those in ultrasound-exposed animals. Vindeburnol showed contraversive results of horizontal and vertical activity in both species and generally did not increase locomotor activity. At the same time, the compound showed a specific effect in the FST, significantly reducing the immobility time. Moreover, we found an increase in norepinephrine, dopamine, and its metabolite levels in the brainstem, as well as an increase in dopamine, 3-methoxytyramine, and 3,4-dihydroxyphenylacetic acid levels in the striatum. We also observed a statistically significant increase in tyrosine hydroxylase (TH) levels in the region containing the locus coeruleus (LC). We suggest that using its distinct chemical structure and pharmacological activity as a starting point could boost antidepressant drug discovery.

中文翻译：

Eburnamine 型分子 Vindeburnol 在超声诱发的抑郁症大鼠和小鼠模型中的抗抑郁样作用

Vindeburnol (VIND, RU24722, BC19) 是一种衍生自依布胺-长春胺生物碱组的合成分子，具有许多神经精神药理学作用，但其抗抑郁样作用知之甚少，仅在少数专利中进行了描述。为了可靠地估计这种效应，在雄性 Wistar 大鼠和 BALB/c 小鼠的 20-45 kHz 长期变频超声 (US) 暴露模型中研究了 vindeburnol。 Vindeburnol 在腹膜内 (IP) 剂量 20 mg/kg 同时超声照射的背景下长期施用 Vindeburnol 21 天。通过四项行为测试，即蔗糖偏好测试（SPT）、社交互动测试（SIT）、旷场测试（OFT）和强迫游泳测试（FST），我们发现该化合物的治疗减轻了抑郁样症状。小鼠和大鼠的症状。与暴露于超声波的动物相比，该化合物将小鼠和大鼠中与超声波相关的蔗糖消耗量减少恢复到控制水平，并增加了社交互动时间。 Vindeburnol 在两个物种中显示出相反的水平和垂直活动结果，并且通常不会增加运动活动。同时，该化合物在 FST 中表现出特定的效果，显着减少不动时间。此外，我们发现脑干中去甲肾上腺素、多巴胺及其代谢物水平增加，以及纹状体中多巴胺、3-甲氧基酪胺和3,4-二羟基苯乙酸水平增加。我们还观察到包含蓝斑 (LC) 的区域酪氨酸羟化酶 (TH) 水平显着增加。我们建议，以其独特的化学结构和药理活性为起点可以促进抗抑郁药物的发现。

更新日期：2024-01-12

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