Role of serotonin 5-HT1A receptors in the antidepressant-like effect and the antinociceptive effect of venlafaxine in mice
Role of serotonin 5-HT1A receptors in the antidepressant-like effect and the antinociceptive effect of venlafaxine in mice
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DOI：
10.1017/s1461145708008766
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发表时间：
2009-02-01
影响因子：
4.8
通讯作者：
Mico, Juan A.
中科院分区：
文献类型：
--
作者：
Berrocoso, Esther;Mico, Juan A.
本研究旨在探讨5-HT 1A受体在文拉法辛抗抑郁样作用和抗伤害作用中的作用。为此，研究了选择性5-HT 1A受体拮抗剂（WAY-100635; N-2-[4-（2-甲氧基苯基-1-哌嗪基]乙基]-N-2-吡啶基环己烷甲酰胺）或选择性5-HT 1A受体激动剂（8-OH-DPAT; 8-羟基-2-（二正丙胺）四氢萘氢溴酸盐）与文拉法辛组合在小鼠中通过强迫游泳试验进行研究，一个旨在筛选潜在抗抑郁药的范例，以及热板试验，一个阶段性疼痛模型。令人惊讶的是，结果显示WAY-100635大大降低了文拉法辛的抗抑郁样作用，而8-OH-DPAT使这种抗抑郁药的无效剂量有效。然而，在热板试验中，WAY-100635显着增强文拉法辛的抗伤害作用，而8-OH-DPAT抵消其抗伤害作用。这些发现表明，5-HT 1A受体在调节文拉法辛的抗抑郁样和抗伤害性作用中发挥不同的作用。结果表明，阻断前脑中的5-HT 1A受体将抵消中缝核水平的有利（抗抑郁样）作用，因此，所证明的总体作用是拮抗作用。这表明位于前脑区域的5-HT 1A受体在抗抑郁样作用中起主导作用。相反，文拉法辛的抗伤害性作用可能是由于在相同的中缝核中的体树突5-HT 1A受体的阻断而增强的，促进了下行的单胺能疼痛控制系统。
The present study was undertaken to evaluate the potential role of 5-HT1A receptors in the antidepressant-like effect and antinociceptive effect of venlafaxine. With this aim, the effect of either a selective 5-HT1A receptor antagonist (WAY-100635; N-2-[4-(2-methoxyphenyl-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexane carboxamide) or a selective 5-HT1A receptor agonist (8-OH-DPAT; 8-hydroxy-2-(di-n-propylamine) tetralin hydrobromide) was investigated in mice in combination with venlafaxine by means of the forced swimming test, a paradigm aimed at screening potential antidepressants, and the hot-plate test, a phasic pain model. Surprisingly, the results showed that WAY-100635 produced a large decrease in the antidepressant-like effect of venlafaxine, while 8-OH-DPAT rendered effective a non-effective dose of this antidepressant. However, in the hot-plate test WAY-100635 significantly enhanced the antinociceptive effect of venlafaxine, whereas 8-OH-DPAT counteracted its antinociceptive effect. These findings show that 5-HT1A receptors play differing roles in modulating the antidepressant-like and antinociceptive effects of venlafaxine in the models investigated. The results imply that blockade of the 5-HT1A receptors in the forebrain will counteract the favourable (antidepressant-like) effect at raphe nuclei level, and consequently, the overall effect evidenced is an antagonism. This suggests a predominant role of 5-HT1A receptors located in the forebrain area for the antidepressant-like effect. In contrast, the antinociceptive effect of venlafaxine is probably potentiated due to the blockade of somatodendritic 5-HT1A receptors in the same raphe nuclei, facilitating the descending monoaminergic pain control system.