1 University of Guelph, Guelph, Canada.
2 Laboratory of Addictive Diseases, Rockefeller University, New York, USA.
J Psychopharmacol. 2017 Dec;31(12):1605-1614. doi: 10.1177/0269881117732515. Epub 2017 Oct 26.
Pre-clinical and clinical evidence suggests that the antidepressant efficacy of the selective serotonin reuptake inhibitor escitalopram can be enhanced by the dopamine and serotonin partial agonist aripiprazole. Given the range of possible neurochemical interactions between these drugs, the current study investigated whether aripiprazole alters the hedonic and psychomotor effects of escitalopram. Male Sprague Dawley rats ( n=116) received 10 mg/kg/day escitalopram (subcutaneous), 2 mg/kg/day aripiprazole (subcutaneous), or combined aripiprazole + escitalopram, and were tested for consumption of incentive nutritional stimuli (high-fructose corn syrup and chow), stereotypy and locomotor activity. At the conclusion of behavioral testing, mRNAs of two genes involved in reward processes were quantified: hypothalamic pro-opiomelanocortin and hippocampal brain-derived neurotrophic factor. Escitalopram produced a selective, but temporary, decrease in high fructose corn syrup consumption that was not altered by aripiprazole co-administration. Escitalopram had no significant effect on locomotion, but aripiprazole co-administration produced a persistent increase in stereotypy. Both brain-derived neurotrophic factor and pro-opiomelanocortin mRNA levels were lower in the aripiprazole + escitalopram group relative to the escitalopram group. Taken together, these results suggest that aripiprazole may enhance the antidepressant efficacy of escitalopram through improvement of psychomotor functions.
临床前和临床证据表明，选择性 5-羟色胺再摄取抑制剂艾司西酞普兰的抗抑郁疗效可以通过多巴胺和 5-羟色胺部分激动剂阿立哌唑增强。鉴于这些药物之间可能存在的神经化学相互作用，本研究调查了阿立哌唑是否会改变艾司西酞普兰的愉悦和精神运动效应。雄性 Sprague Dawley 大鼠（n=116）接受 10 mg/kg/天艾司西酞普兰（皮下注射）、2 mg/kg/天阿立哌唑（皮下注射）或联合阿立哌唑+艾司西酞普兰，并接受激励性营养刺激（高果糖玉米糖浆和饲料）、刻板行为和运动活动的测试。在行为测试结束时，量化了两个参与奖励过程的基因的 mRNA：下丘脑促阿黑皮素原和海马脑源性神经营养因子。艾司西酞普兰选择性地但暂时降低了高果糖玉米糖浆的消耗，而阿立哌唑联合给药并没有改变这一结果。艾司西酞普兰对运动没有显著影响，但阿立哌唑联合给药会导致刻板行为持续增加。与艾司西酞普兰组相比，阿立哌唑+艾司西酞普兰组的脑源性神经营养因子和促阿黑皮素原 mRNA 水平均较低。总的来说，这些结果表明，阿立哌唑可能通过改善精神运动功能增强艾司西酞普兰的抗抑郁疗效。
