Ripoll Nadège, David Denis Joseph Paul, Dailly Eric, Hascoët Martine, Bourin Michel
Faculté de Médecine, EA 3256 Neurobiologie de l'anxiété et de la dépression, BP 53508, 1 rue Gaston Veil, F44035 Nantes, Cedex 01, France.
Behav Brain Res. 2003 Aug 14;143(2):193-200. doi: 10.1016/s0166-4328(03)00034-2.
Several studies have reported rodent strain differences in the response to antidepressants in animal models of depression. The aim of the present study was to investigate the potential contribution of genetic factors to antidepressant response in an animal model of depression: the tail suspension test (TST). For this study four mice strains (Swiss and NMRI, two outbred strains and DBA/2 and C57BL/6J Rj, two inbred strains) were submitted to the TST after acute administration of five antidepressants: the tricyclic antidepressants (TCAs) imipramine and desipramine, the selective serotonin (5-HT) reuptake inhibitors (SSRIs) paroxetine and citalopram and the dopamine reuptake inhibitor bupropion. The C57BL/6J Rj strain had a longer baseline immobility time in comparison to the other strains. All antidepressants studied in this work decreased immobility time in the Swiss and C57BL/6J Rj strains. However, the Swiss strain displayed greater sensitivity to citalopram (from 2mg/kg) and C57BL/6J Rj to paroxetine (from 0.5mg/kg). This latter presented a greater size-effect with citalopram than with other strains and reached more than 60% from 8mg/kg. Moreover the size-effect of desipramine, paroxetine and bupropion in Swiss mice was greater than in the other strains in the TST. The NMRI and DBA/2 mice only responded to 5-HT reuptake inhibitors, both selective (paroxetine, citalopram) or non-selective (imipramine). The NMRI strain was more sensitive to imipramine and presented a size-effect (43% at 8mg/kg) superior to those of other strains. DBA/2 strain was more sensitive to citalopram than paroxetine and imipramine. Our results suggest that response to an antidepressant treatment is under control of genetic factors and that the strain of mouse is an important parameter to consider.
多项研究报告了在抑郁症动物模型中，啮齿动物品系对抗抑郁药的反应存在差异。本研究的目的是在抑郁症动物模型——悬尾试验（TST）中，探究遗传因素对抗抑郁反应的潜在影响。在本研究中，对四种小鼠品系（瑞士小鼠和NMRI小鼠，两种远交系；以及DBA/2小鼠和C57BL/6J Rj小鼠，两种近交系）急性给予五种抗抑郁药后进行悬尾试验：三环类抗抑郁药（TCA）丙咪嗪和地昔帕明、选择性5-羟色胺（5-HT）再摄取抑制剂（SSRI）帕罗西汀和西酞普兰，以及多巴胺再摄取抑制剂安非他酮。与其他品系相比，C57BL/6J Rj品系的基线不动时间更长。本研究中所研究的所有抗抑郁药均能减少瑞士小鼠和C57BL/6J Rj品系的不动时间。然而，瑞士品系对西酞普兰（从2mg/kg起）表现出更高的敏感性，而C57BL/6J Rj品系对帕罗西汀（从0.5mg/kg起）更为敏感。后者对西酞普兰的量效作用比其他品系更大，在8mg/kg时达到60%以上。此外，在悬尾试验中，地昔帕明、帕罗西汀和安非他酮对瑞士小鼠的量效作用大于其他品系。NMRI小鼠和DBA/2小鼠仅对5-HT再摄取抑制剂有反应，包括选择性（帕罗西汀、西酞普兰）或非选择性（丙咪嗪）抑制剂。NMRI品系对丙咪嗪更为敏感，其量效作用（8mg/kg时为43%）优于其他品系。DBA/2品系对西酞普兰比对帕罗西汀和丙咪嗪更为敏感。我们的结果表明，对抗抑郁治疗的反应受遗传因素控制，小鼠品系是一个需要考虑的重要参数。
