Prica Corina, Hascoet Martine, Bourin Michel
EA 3256 Neurobiologie de l'anxiété et de la dépression, Faculté de Médecine 1, rue Gaston Veil BP 53508, 44035 Nantes cedex 01, France.
Behav Brain Res. 2008 Dec 1;194(1):92-9. doi: 10.1016/j.bbr.2008.06.028. Epub 2008 Jul 4.
The monoamine hypothesis based on the deficiency of one or several monoamines is commonly evoked to explain the physiopathology of depression. This hypothesis initially based on noradrenalin and serotonin deficiency has been extended to dopamine. The animal models of depression also suggest an implication of dopamine in the physiopathology of depression. The forced swimming test is an animal model used to predict the antidepressant activity of drugs.
The scope of this study was to investigate the antidepressant-like effect of a dopamine re-uptake inhibitor, bupropion, when combined with conventional antidepressants drugs SSRIs (selective serotonin re-uptake inhibitors), SNRI (selective serotonin-noradrenalin re-uptake inhibitors) and a NRI (selective noradrenalin inhibitor).
This study assessed the effects of co-administration of bupropion with SSRIs: sertraline, paroxetine, citalopram, fluvoxamine, SNRIs: venlafaxine and milnacipran and NRI: desipramine, using an animal model of depression, the forced swimming test in mice. Subactive doses of bupropion (4 and 8mg/kg) and antidepressants: sertraline (2mg/kg), paroxetine, citalopram, fluvoxamine, venlafaxine, milnacipran and desipramine (4mg/kg) were given i.p. 45 and 30min, respectively, before the test.
Bupropion (4 and 8mg/kg) combined with inactive doses of antidepressants, decreased immobility time in the mice FST except with sertraline and desipramine. In conclusion, the antidepressant-enhancing effects of bupropion, in the present study, are in agreement with preliminary clinical evidence suggesting that bupropion may enhance the efficacy of therapeutic effect of SSRIs and SNRIs but not the therapeutic effect of NRI. These results suggest that bupropion enhances only the serotonergic system.
基于一种或几种单胺缺乏的单胺假说常被用来解释抑郁症的病理生理学。该假说最初基于去甲肾上腺素和5-羟色胺缺乏，现已扩展到多巴胺。抑郁症的动物模型也表明多巴胺参与了抑郁症的病理生理学过程。强迫游泳试验是一种用于预测药物抗抑郁活性的动物模型。
本研究的范围是调查多巴胺再摄取抑制剂安非他酮与传统抗抑郁药物选择性5-羟色胺再摄取抑制剂（SSRI）、5-羟色胺-去甲肾上腺素再摄取抑制剂（SNRI）和去甲肾上腺素再摄取抑制剂（NRI）联合使用时的抗抑郁样作用。
本研究使用小鼠强迫游泳试验这一抑郁症动物模型，评估了安非他酮与SSRI（舍曲林、帕罗西汀、西酞普兰、氟伏沙明）、SNRI（文拉法辛和米氮平）以及NRI（地昔帕明）联合给药的效果。在试验前45分钟和30分钟分别腹腔注射亚有效剂量的安非他酮（4毫克/千克和8毫克/千克）和抗抑郁药：舍曲林（2毫克/千克）、帕罗西汀、西酞普兰、氟伏沙明、文拉法辛、米氮平以及地昔帕明（4毫克/千克）。
安非他酮（4毫克/千克和8毫克/千克）与无活性剂量的抗抑郁药联合使用，可减少小鼠强迫游泳试验中的不动时间，但与舍曲林和地昔帕明联合使用时除外。总之，在本研究中，安非他酮的抗抑郁增强作用与初步临床证据一致，表明安非他酮可能增强SSRI和SNRI的治疗效果，但不能增强NRI的治疗效果。这些结果表明安非他酮仅增强5-羟色胺能系统。
