Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland.
Pharmacol Rep. 2009 Nov-Dec;61(6):1050-60. doi: 10.1016/s1734-1140(09)70167-7.
Considerable attention has been paid to a possible role of immunological dysregulation in the pathogenesis of depression. It has been reported that combined administration of antidepressant drugs and the non-competitive NMDA receptor antagonist amantadine reduces immobility time in the forced swimming test (FST). Moreover, preliminary clinical data show that such a combination of drugs has a beneficial effect on treatment-resistant depressed patients. Since immune activation and a pro-inflammatory response are clearly evident in treatment-resistant depression, the aim of the present study was to examine the effect of a combination of the antidepressant fluoxetine and amantadine on immunoendocrine parameters in rats subjected to the forced swimming test. The obtained results revealed synergistic antidepressant effects of the combined administration of fluoxetine (10 mg/kg) and amantadine (10 mg/kg) - drugs otherwise ineffective when given separately in the above doses. Antidepressant activity was accompanied with a significant decrease in the capacity of splenocytes to proliferate in response to concanavalin A. Moerover, fluoxetine and the combination of amantadine and fluoxetine reduced relative spleen weight in rats subjected to the FST, compared to rats treated with the vehicle. The combination of amantadine and fluoxetine enhanced the production of the negative immunoregulator interleukin-10 (but not interferon-gamma) in rats subjected to the FST. The exposure to the FST produced an increase in plasma corticosterone levels, which was significantly attenuated by pretreatment with fluoxetine and amantadine. In summary, the antidepressive efficacy of a combination of fluoxetine and amantadine given in suboptimal doses may be related to the negative immunoendocrine effects of these drugs.
人们已经关注到免疫失调在抑郁症发病机制中的可能作用。有报道称，抗抑郁药联合非竞争性 NMDA 受体拮抗剂金刚烷胺可减少强迫游泳试验（FST）中的不动时间。此外，初步临床数据显示，这种药物联合使用对治疗抵抗性抑郁患者有有益的效果。由于免疫激活和促炎反应在治疗抵抗性抑郁症中非常明显，因此本研究的目的是研究抗抑郁药氟西汀和金刚烷胺联合给药对强迫游泳试验大鼠免疫内分泌参数的影响。结果表明，氟西汀（10mg/kg）和金刚烷胺（10mg/kg）联合给药具有协同抗抑郁作用，而这两种药物在上述剂量下单独给药则无效。抗抑郁作用伴随着脾细胞对刀豆蛋白 A 增殖反应能力的显著下降。此外，与用载体处理的大鼠相比，氟西汀和金刚烷胺联合给药以及氟西汀降低了 FST 大鼠的相对脾脏重量。金刚烷胺和氟西汀联合给药增强了 FST 大鼠负免疫调节剂白细胞介素-10（而非干扰素-γ）的产生。强迫游泳会导致血浆皮质酮水平升高，氟西汀和金刚烷胺预处理可显著减弱这种升高。综上所述，亚最佳剂量的氟西汀和金刚烷胺联合给药的抗抑郁疗效可能与这些药物的负免疫内分泌作用有关。
