Effects of sustained administration of the serotonin and norepinephrine reuptake inhibitor venlafaxine:: II.: In vitro studies in the rat
Effects of sustained administration of the serotonin and norepinephrine reuptake inhibitor venlafaxine:: II.: In vitro studies in the rat
复制标题
DOI：
10.1016/s0028-3908(00)00018-6
复制
发表时间：
2000-01-01
影响因子：
4.7
通讯作者：
Debonnel, G
中科院分区：
文献类型：
--
作者：
Béïque, JC;de Montigny, C;Debonnel, G
长期服用低剂量(10 mg/kg/d)和大剂量(40 mg/kg/d)的双重5-羟色胺和去甲肾上腺素再摄取抑制剂文拉法辛(S.C.用[H-3]5-羟色胺或[H-3]NE预负荷的海马片在去除微泵后48h电诱发氚的释放。高剂量的文拉法辛可促进电诱发的[H-3]5-羟色胺的释放，而大剂量的文拉法辛不能改变电诱发的去甲肾上腺素的释放。小剂量文拉法辛不改变5-HT1B激动剂CP 93、129对电诱发的[H-3]5-羟色胺释放的抑制作用，而大剂量文拉法辛使其减弱，提示5-HT1B末端自身受体的功能性脱敏。令人意外的是，文拉法辛两种方案都没有改变UK 14,304对电诱发的[H-3]5-羟色胺和[H-3]NE释放的抑制作用，这表明α(2)-肾上腺素能自体受体和异型受体都没有脱敏。最后，对5-羟色胺和去甲肾上腺素再摄取过程的功能进行了评估。各治疗方案均不改变大鼠海马片和中脑片对[H-3]5-羟色胺的基础摄取，也不改变海马片对[H-3]NE的摄取。灌流液中1MU M的帕罗西汀对文拉法辛40 mg/kg/d灌流21d的大鼠海马脑片[H-3]5-羟色胺的电释放无明显促进作用。综上所述，这些结果表明，就末端5-HT1B自体受体、α(2)-肾上腺素能自体和异型受体的敏感性改变而言，长期服用文拉法辛的效果与经典的SSRI没有什么不同。(C)2000爱思唯尔科学有限公司。保留所有权利。
The effects of long-term administrations of a low (10 mg/kg/day) and a high (40 mg/kg/day) dose of the dual 5-HT and NE reuptake inhibitor venlafaxine (delivered s.c. by osmotic minipumps for 21 days) were assessed on the electrically-evoked release of tritium from hippocampal slices preloaded with either [H-3]5-HT or [H-3]NE, 48 h after the removal of the minipump. The high, but not the low, dose regimen of venlafaxine enhanced the electrically-evoked release of [H-3]5-HT while treatment with the high dose of venlafaxine failed to alter the electrically-evoked release of [H-3]NE. The inhibitory effect of the 5-HT1B agonist CP 93,129 on the electrically evoked release of [H-3]5-HT was unaltered by the low dose regimen of venlafaxine;while it was attenuated in rats treated with the high dose of venlafaxine, indicative of a functional desensitization of the terminal 5-HT1B autoreceptor. Unexpectedly, neither regimen of venlafaxine altered the inhibitory effect of UK 14,304 on the electrically evoked release of both [H-3]5-HT and [H-3]NE, indicating that neither the alpha(2)-adrenergic auto- nor heteroreceptors were desensitized. Finally, the functions of the 5-HT and NE reuptake process were assessed. None of the treatment regimens altered the basal uptake of [H-3]5-HT from hippocampal or mesencephalic slices nor that of [H-3]NE from hippocampal slices. Finally, the enhancing effect of 1 mu M of paroxetine in the perfusion medium on the electrical release of [H-3]5-HT was unaltered in hippocampal slices prepared from rats that had been treated for 21 days with 40 mg/kg/day of venlafaxine. Taken together, these results indicate that, in terms of alteration of the sensitivity of the terminal 5-HT1B autoreceptor, alpha(2)-adrenergic auto-and heteroreceptors, the effects of long-term administration of venlafaxine are no different than those observed with classical SSRI's. (C) 2000 Elsevier Science Ltd. All rights reserved.