The widely-used anti-viral drug interferon-alpha induces depressive- and anxiogenic-like effects in healthy rats
The widely-used anti-viral drug interferon-alpha induces depressive- and anxiogenic-like effects in healthy rats
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DOI：
10.1016/j.bbr.2007.05.005
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发表时间：
2007-08-22
影响因子：
2.7
通讯作者：
O'Mara, Shane M.
中科院分区：
文献类型：
--
作者：
Fahey, Briana;Hickey, Barry;O'Mara, Shane M.
干扰素-α（IFN-α）是一种天然存在的人类细胞因子，是治疗几种病毒性疾病和癌症的关键疗法。然而，治疗可产生显著的神经精神和神经毒性不良事件，包括抑郁和焦虑。在这里，我们研究了临床上相当的治疗方案的干扰素-α对抑郁和焦虑样行为的大鼠的影响，也检查了额叶皮质和海马BDNF水平。用IFN-α治疗四周的大鼠表现出抑郁和焦虑样行为的显着增加。进一步的实验研究显示，享乐失调（对甜味溶液的更强偏好）直到治疗的第二周才出现，并且随着治疗的进展变得更加持久。没有发现IFN-α诱导的BDNF水平的显著变化。这些结果表明，在患者中观察到的情感缺陷可以在健康动物中模拟。该模型可能是一种新的工具，调查的程度和机制的IFN-α精神综合征。(c)2007年由Elsevier B. V.出版。
Interferon-alpha (IFN-alpha) is a naturally occurring human cytokine that is a key therapy in the treatment of several viral diseases and cancers. However, treatment can produce significant neuropsychiatric and neurotoxic adverse events, including depression and anxiety. Here we investigated the effects of a clinically-comparable treatment regime of IFN-alpha on depressive- and anxiety-like behaviour in rats; and also examined frontal-cortical and hippocampal BDNF levels. Rats treated with IFN-alpha for four weeks showed significant increases in depressive- and anxiety-like behaviour. Further experimental investigation revealed that hedonic dysregulation (stronger preference for a sweet solution) did not emerge until the second week of treatment, and became more persistent as treatment progressed. No significant IFN-alpha-induced changes in BDNF levels were found. These results indicate that the affective deficits seen in patients may be modelled in healthy animals. This model may represent a novel tool to investigate the extent of and mechanisms underlying the IFN-a psychiatric syndrome. (c) 2007 Published by Elsevier B.V.