O'Mahony Siobhain M, Myint Aye-Mu, Steinbusch Harry, Leonard Brian E
Department of Psychiatry and Neuropsychology, University of Maastricht, Maastricht, The Netherlands.
Neuroimmunomodulation. 2005;12(5):293-8. doi: 10.1159/000087107.
Efavirenz is a non-nucleoside reverse transcriptase inhibitor that is used in the treatment of the HIV-1 variant. Adverse central nervous system side effects such as headache, dizziness, insomnia, fatigue, severe depression and suicidal ideation are noted in patients receiving efavirenz. In this study, the effects of efavirenz on changes in behaviour and on some pro- and anti-inflammatory cytokines in Wistar rats were studied to assess whether efavirenz causes depressive symptoms via the cytokine network and, if so, whether antidepressant therapy known to attenuate the effects of pro-inflammatory cytokines could prevent these changes. The efavirenz-treated rats displayed spatial memory deficits in the Morris water maze. These rats also appeared to be more susceptible to stress than the other groups as seen by an increase in the latency to emerge in the home cage emergence test following the stress of the Morris water maze. The concentrations of pro-inflammatory cytokines interleukin-1 beta and tumour necrosis factor-alpha were also significantly higher in the efavirenz group. The antidepressant paroxetine reduced the susceptibility to stress and prevented such an increase in pro-inflammatory cytokines. It is concluded that efavirenz induces depressive-like behaviour in the rat and a susceptibility to stress, which are accompanied by an increase in pro-inflammatory cytokines. These symptoms are partially alleviated by chronic treatment with paroxetine.
依非韦伦是一种用于治疗HIV-1变体的非核苷类逆转录酶抑制剂。接受依非韦伦治疗的患者会出现不良的中枢神经系统副作用，如头痛、头晕、失眠、疲劳、严重抑郁和自杀意念。在本研究中，研究了依非韦伦对Wistar大鼠行为变化以及一些促炎和抗炎细胞因子的影响，以评估依非韦伦是否通过细胞因子网络导致抑郁症状，如果是，已知可减轻促炎细胞因子作用的抗抑郁治疗是否可以预防这些变化。接受依非韦伦治疗的大鼠在莫里斯水迷宫中表现出空间记忆缺陷。在莫里斯水迷宫应激后进行的家笼出现试验中，这些大鼠出现的潜伏期增加，这表明它们似乎比其他组更容易受到应激影响。依非韦伦组中促炎细胞因子白细胞介素-1β和肿瘤坏死因子-α的浓度也显著更高。抗抑郁药帕罗西汀降低了对应激的易感性，并防止了促炎细胞因子的这种增加。得出的结论是，依非韦伦在大鼠中诱导出类似抑郁的行为和对应激的易感性，同时伴有促炎细胞因子的增加。帕罗西汀的长期治疗可部分缓解这些症状。
