Sànchez C
Pharmacological Research, Lundbeck A / S, Valby-Copenhagen, Denmark.
Eur J Pharmacol. 1997 Sep 10;334(2-3):127-32. doi: 10.1016/s0014-2999(97)01199-0.
Recently published studies have suggested that behavioral and neurochemical changes induced by selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors are potentiated by coadministration of a 5-HT1A receptor antagonist. The potentiating effect is hypothesized to be due to antagonism of somatodendritic 5-HT1A autoreceptors. In the present study the effects of concomitant administration of a selective 5-HT reuptake inhibitor with a 5-HT1A receptor antagonist (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-N-(2-pyridinyl) cyclo-hexanecarboxamide (WAY 100635) or a beta-adrenoceptor and 5-HT1A/1B receptor antagonist (pindolol or (-)-penbutolol) were studied in isolated aggressive mice. WAY 100635 was inactive, but high doses of WAY 100635 produced a marked anti-aggressive effect when combined with a non-effective dose of citalopram or paroxetine. Low doses of pindolol, but not (-)-penbutolol, produced a minor but significant anti-aggressive effect in combination with citalopram or paroxetine. High doses of pindolol or (-)-penbutolol inhibited aggressive behavior, an effect which was reversed by citalopram or paroxetine. The beta-adrenoceptor antagonist, metoprolol, but not the alpha1-adrenoceptor antagonist, prazosin, facilitated the anti aggressive effect of citalopram. The significance of these findings is discussed relative to the above hypothesis.
最近发表的研究表明，选择性5-羟色胺（5-羟色胺，5-HT）再摄取抑制剂引起的行为和神经化学变化，会因联合使用5-HT1A受体拮抗剂而增强。据推测，这种增强作用是由于躯体树突状5-HT1A自身受体的拮抗作用。在本研究中，在分离的攻击性小鼠中研究了选择性5-HT再摄取抑制剂与5-HT1A受体拮抗剂（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（WAY 100635）或β-肾上腺素能受体和5-HT1A/1B受体拮抗剂（吲哚洛尔或(-)-喷布洛尔）联合给药的效果。WAY 100635无活性，但高剂量的WAY 100635与无效剂量的西酞普兰或帕罗西汀联合使用时，产生了显著的抗攻击作用。低剂量的吲哚洛尔而非(-)-喷布洛尔，与西酞普兰或帕罗西汀联合使用时产生了轻微但显著的抗攻击作用。高剂量的吲哚洛尔或(-)-喷布洛尔抑制攻击行为，这种作用被西酞普兰或帕罗西汀逆转。β-肾上腺素能受体拮抗剂美托洛尔而非α1-肾上腺素能受体拮抗剂哌唑嗪，促进了西酞普兰的抗攻击作用。相对于上述假设，讨论了这些发现的意义。
