Wolff M C, Leander J D
Lilly Research Laboratories, Eli Lilly, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Eur J Pharmacol. 1998 Mar 12;345(1):35-9. doi: 10.1016/s0014-2999(98)00052-1.
The effects of two selective serotonin reuptake inhibitors, fluoxetine and citalopram, and a nonselective monoamine reuptake inhibitor, imipramine, were characterized in pigeons that had been trained to discriminate 0.64 mg/kg of 8-hydroxy-(2-di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), a 5-HT1A receptor agonist, from saline. Neither fluoxetine, citalopram, nor imipramine generalized to the 8-OH-DPAT-induced stimulus cue. However, when administered in addition to 8-OH-DPAT, both fluoxetine (10 mg/kg) and citalopram (10 mg/kg) lowered the ED50 for generalization of 8-OH-DPAT from 0.16 mg/kg (8-OH-DPAT by itself) to 0.05 mg/kg (fluoxetine + 8-OH-DPAT) and 0.06 mg/kg (citalopram + 8-OH-DPAT). Under similar conditions, imipramine (1 mg/kg) had no effect on the generalization curve for 8-OH-DPAT. The data support the hypothesis that activation of the 5-HT1A receptor may be relevant to the mechanism of action of serotonin reuptake inhibitors.
在已训练能够区分0.64毫克/千克的8-羟基-（2-二正丙基氨基）四氢溴化萘（8-OH-DPAT，一种5-HT1A受体激动剂）与生理盐水的鸽子中，对两种选择性5-羟色胺再摄取抑制剂氟西汀和西酞普兰以及一种非选择性单胺再摄取抑制剂丙咪嗪的作用进行了表征。氟西汀、西酞普兰和丙咪嗪均未对8-OH-DPAT诱导的刺激线索产生泛化作用。然而，当与8-OH-DPAT联合给药时，氟西汀（10毫克/千克）和西酞普兰（10毫克/千克）均将8-OH-DPAT泛化的半数有效剂量（ED50）从0.16毫克/千克（单独使用8-OH-DPAT）降低至0.05毫克/千克（氟西汀 + 8-OH-DPAT）和0.06毫克/千克（西酞普兰 + 8-OH-DPAT）。在类似条件下，丙咪嗪（1毫克/千克）对8-OH-DPAT的泛化曲线没有影响。这些数据支持了5-HT1A受体的激活可能与5-羟色胺再摄取抑制剂的作用机制相关的假说。
