Chronic unpredictable stress induces a cognitive deficit and anxiety-like behavior in rats that is prevented by chronic antidepressant drug treatment
Chronic unpredictable stress induces a cognitive deficit and anxiety-like behavior in rats that is prevented by chronic antidepressant drug treatment
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DOI：
10.1038/sj.npp.1301410
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发表时间：
2008-01-01
影响因子：
7.6
通讯作者：
Morilak, David A.
中科院分区：
文献类型：
--
作者：
Bondi, Corina O.;Rodriguez, Gustavo;Morilak, David A.
慢性压力是人类许多精神病理疾病发展的危险因素，包括重度抑郁症和焦虑症。抑郁和焦虑的共病程度很高。此外，与额叶功能障碍相关的认知障碍，包括认知转移和行为灵活性缺陷，越来越多地被认为是抑郁症、焦虑症和其他与压力相关的精神疾病的主要组成部分。为了开始了解慢性压力的认知和情绪后果背后的神经生物学机制，有必要采用表现出类似效果的动物模型。在本研究中，慢性不可预测压力（CUS）的大鼠模型在注意力设定转移测试中始终诱发超维度设定转移能力的认知障碍，这表明内侧前额叶皮层的功能发生了改变。 CUS 还增加了高架十字迷宫中的焦虑样行为。此外，在 CUS 治疗前 1 周开始并持续整个行为测试期，使用选择性去甲肾上腺素再摄取阻滞剂地昔帕明（7.5 毫克/公斤/天）和选择性 5-羟色胺再摄取阻滞剂艾司西酞普兰（10 毫克/公斤/天）进行长期治疗，并持续到行为测试期，可防止 CUS 引起的超维度设定转移缺陷。长期地昔帕明治疗还可以防止 CUS 诱导的十字迷宫中焦虑样行为反应性的增加，但艾司西酞普兰在这方面效果较差。因此，CUS 会引起认知和情绪障碍，类似于重度抑郁症和焦虑症的组成部分。这些影响可以通过抗抑郁药物的长期治疗来预防，这也与抗抑郁药物治疗可以预防抑郁发作复发的临床证据相一致。
Chronic stress is a risk factor for the development of many psychopathological conditions in humans, including major depression and anxiety disorders. There is a high degree of comorbidity of depression and anxiety. Moreover, cognitive impairments associated with frontal lobe dysfunction, including deficits in cognitive set-shifting and behavioral flexibility, are increasingly recognized as major components of depression, anxiety disorders, and other stress-related psychiatric illnesses. To begin to understand the neurobiological mechanisms underlying the cognitive and emotional consequences of chronic stress, it is necessary to employ an animal model that exhibits similar effects. In the present study, a rat model of chronic unpredictable stress (CUS) consistently induced a cognitive impairment in extradimensional set shifting capability in an attentional set shifting test, suggesting an alteration in function of the medial prefrontal cortex. CUS also increased anxiety-like behavior on the elevated plus-maze. Further, chronic treatment both with the selective norepinephrine reuptake blocker, desipramine (7.5 mg/kg/day), and the selective serotonin reuptake blocker, escitalopram (10 mg/kg/day), beginning 1 week before CUS treatment and continuing through the behavioral testing period, prevented the CUS-induced deficit in extradimensional set-shifting. Chronic desipramine treatment also prevented the CUS-induced increase in anxiety-like behavioral reactivity on the plus-maze, but escitalopram was less effective on this measure. Thus, CUS induced both cognitive and emotional disturbances that are similar to components of major depression and anxiety disorders. These effects were prevented by chronic treatment with antidepressant drugs, consistent also with clinical evidence that relapse of depressive episodes can be prevented by antidepressant drug treatment.