Myint A M, O'Mahony S, Kubera M, Kim Y K, Kenny C, Kaim-Basta A, Steinbusch H W M, Leonard B E
University of Maastricht, MD Maastricht, The Netherlands.
J Psychopharmacol. 2007 Nov;21(8):843-50. doi: 10.1177/0269881107077165.
Treatment with pro-inflammatory cytokine, IFNalpha was documented to result in neuropsychiatric complications including depression and treatment with antidepressant, paroxetine could improve the depressive symptoms. Therefore, the effects of IFNalpha on behaviour and cytokine changes in the whole blood culture and in the prefrontal cortex, hypothalamus and hippocampus areas of the brain in wistar rats were investigated with emphasis on the role of paroxetine in the prevention of depressive behaviour induced by pro-inflammatory cytokines. The group of rats treated with IFNalpha (s.c. 50,000 IU/kg for 3 days/week for 5 weeks) was compared with three other groups; 1) saline control group (s.c. normal saline 0.2 ml/kg/day for 7 weeks), 2) paroxetine control group (paroxetine suspension orally 10 mg/kg/day for 7 weeks) and 3) group treated with paroxetine for 2 weeks followed by IFNalpha for 5 weeks. In open filed, the IFNalpha treated rats showed anxiety behaviour compared to the rats from the other groups. There was no significant difference in home cage emergence test, Morris water maze and object recognition test. There is no significant difference in plasma corticosterone between groups. The pro-inflammatory cytokines (TNFalpha, IL1beta and IFNgamma), were significantly higher whereas the anti-inflammatory cytokine, IL10 was lower in the stimulated whole blood culture of IFNalpha treated rats. In the brain, both pro-inflammatory cytokine IL1beta and anti-inflammatory cytokine IL10 were higher in hypothalamus of the IFNalpha treated rats; by contrast the concentration of IL10 was lowest in hippocampus region of this group compared to the other groups. The paroxetine pretreated rats did not show these cytokine changes following IFNalpha treatment. Thus it appears that paroxetine pretreatment prevents the pro-inflammatory changes in blood and brain following IFNalpha treatment in turn prevents the anxiety behaviour.
有文献记载，用促炎细胞因子干扰素α进行治疗会导致包括抑郁症在内的神经精神并发症，而用抗抑郁药帕罗西汀进行治疗可以改善抑郁症状。因此，研究了干扰素α对Wistar大鼠全血培养物以及大脑前额叶皮质、下丘脑和海马区行为及细胞因子变化的影响，重点关注帕罗西汀在预防促炎细胞因子诱导的抑郁行为中的作用。将用干扰素α治疗的大鼠组（皮下注射50,000 IU/kg，每周3天，共5周）与其他三组进行比较；1）生理盐水对照组（皮下注射0.2 ml/kg/天的生理盐水，共7周），2）帕罗西汀对照组（口服10 mg/kg/天的帕罗西汀悬浮液，共7周），3）先用帕罗西汀治疗2周，然后用干扰素α治疗5周的组。在旷场实验中，与其他组的大鼠相比，用干扰素α治疗的大鼠表现出焦虑行为。在旷笼实验、莫里斯水迷宫实验和物体识别实验中没有显著差异。各组之间血浆皮质酮没有显著差异。在用干扰素α治疗的大鼠的刺激全血培养物中，促炎细胞因子（肿瘤坏死因子α、白细胞介素1β和干扰素γ）显著升高，而抗炎细胞因子白细胞介素10则降低。在大脑中，在用干扰素α治疗的大鼠的下丘脑中，促炎细胞因子白细胞介素1β和抗炎细胞因子白细胞介素10都较高；相比之下，与其他组相比，该组海马区白细胞介素10的浓度最低。帕罗西汀预处理的大鼠在接受干扰素α治疗后没有出现这些细胞因子变化。因此，似乎帕罗西汀预处理可预防干扰素α治疗后血液和大脑中的促炎变化，进而预防焦虑行为。
