Abstract

Introduction

Antidepressants increase the level of 5-HT in the somatodendritic region of the serotonergic dorsal raphe nucleus (DRN) neurons in the first few days of their usage, which, in turn, inhibits the serotonergic neurons locally. Pindolol may eliminate this inhibition when used in combination with antidepressants.

Material and methods

We aimed to determine the effect of pindolol on 5-HT1A receptor response in the DRN neurons, using voltage clamp recordings and prove the potentiation of antidepressant effect of venlafaxine by pindolol through behavior experiments. Balb/c mice, 28–35 days-old were used.

Results

5-HT application (25 µM) induced an outward current by 23.36 ± 3.79 pA at the neurons in the dorsal subnucleus of DRN. This effect was inhibited by pre-administration of WAY-100135 (21 µM) and pindolol (10 µM) separately. The current induced by 5-HT and 8-OHDPAT have no statistically significance. 8-OHDPAT (30 µM) induced a 5-HT-like outward current, which was inhibited by pre-administration of pindolol (10 µM). Combination of venlafaxine (20 mg/kg/day) and pindolol (15 mg/kg/day) significantly reduced immobilization time when compared to the control group in tail suspension test and forced swim test without any significant change in locomotor activity. Administration of venlafaxine (20 mg/kg/day) alone or pindolol (15 mg/kg/day) alone did not significantly reduce immobilization time.

Conclusion

Pindolol has the potential to prevent the inhibition of serotonergic neurons after antidepressant use. Hence, we, for the first time, demonstrated that pindolol can potentiate antidepressant effect of venlafaxine. In the mood disorders, pindolol is likely to increase the effectiveness of antidepressant drugs when given in combination.

中文翻译：

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吲哚洛尔通过抑制小鼠 DRN 神经元 5-HT1A 受体增强文拉法辛的抗抑郁作用

摘要

介绍

抗抑郁药在使用的最初几天会增加 5-羟色胺能背侧中缝核 (DRN) 神经元的体树突区域的 5-HT 水平，这反过来又会局部抑制 5-羟色胺能神经元。当与抗抑郁药联合使用时，吲哚洛尔可以消除这种抑制作用。

材料与方法

我们旨在使用电压钳记录确定吲哚洛尔对 DRN 神经元中 5-HT1A 受体反应的影响，并通过行为实验证明吲哚洛尔对文拉法辛的抗抑郁作用的增强作用。使用 28-35 天大的 Balb/c 小鼠。

结果

5-HT 应用 (25 µM) 在 DRN 背侧亚核的神经元处诱导了 23.36 ± 3.79 pA 的外向电流。分别预先给予 WAY-100135 (21 µM) 和 pindolol (10 µM) 可抑制这种作用。由 5-HT 和 8-OHDPAT 引起的电流没有统计学意义。8-OHDPAT (30 µM) 可诱导 5-HT 样外向电流，该电流可通过预先给予吲哚洛尔 (10 µM) 抑制。与对照组相比，文拉法辛（20 mg/kg/天）和吲哚洛尔（15 mg/kg/天）的组合在悬尾试验和强迫游泳试验中显着减少了固定时间，而运动活动没有任何显着变化。单独使用文拉法辛（20 mg/kg/天）或单独使用吲哚洛尔（15 mg/kg/天）并未显着减少固定时间。

结论

吲哚洛尔有可能在使用抗抑郁药后防止抑制血清素能神经元。因此，我们首次证明了吲哚洛尔可以增强文拉法辛的抗抑郁作用。在情绪障碍中，当联合使用时，吲哚洛尔可能会增加抗抑郁药物的有效性。