A cognitive deficit induced in rats by chronic intermittent cold stress is reversed by chronic antidepressant treatment.
A cognitive deficit induced in rats by chronic intermittent cold stress is reversed by chronic antidepressant treatment.
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DOI：
10.1017/s1461145710000039
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发表时间：
2010-09
期刊：
影响因子：
--
通讯作者：
Morilak DA
中科院分区：
文献类型：
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作者：
Danet M;Lapiz-Bluhm S;Morilak DA
我们此前曾报道，14天的慢性间歇性寒冷(CIC)应激导致大鼠注意定势转移测试中的反转学习认知缺陷。这种作用可能与作为抑郁症认知功能障碍模型的眶前叶皮质5-羟色胺功能失调有关。为了测试慢性抗抑郁药物治疗逆转CIC所致认知功能障碍的能力，首先需要评估CIC所致认知功能障碍的时间特征。因此，在第一项研究中，我们评估了两周CIC应激后认知障碍的持续时间。重复之前的实验，CIC诱导了在最后一次寒冷暴露后3天测试的可逆性学习障碍。然而，在应激治疗结束后7、14或21天的测试中，CIC应激大鼠的认知表现与非应激对照组没有区别。接下来，我们将2周CIC后3天的行为与5周CIC后3天的行为进行了比较，发现反转学习存在类似的缺陷。因此，在最终研究中，在CIC应激2周后开始抗抑郁药物治疗，并在持续CIC应激的同时维持3周。选择性5-羟色胺再摄取抑制剂西酞普兰的慢性和急性治疗，而不是去甲肾上腺素再摄取阻滞剂地昔帕明的治疗，都能逆转CIC应激引起的认知障碍。因此，这种应激诱导的认知缺陷可能是抑郁症中与前额叶皮质活动不足相关的认知障碍的有用模型，并可用于研究慢性抗抑郁药物治疗有益效果的神经生物学机制。
We have previously reported that 14-days of chronic intermittent cold (CIC) stress induced a cognitive deficit in reversal learning on the rat attentional set-shifting test. This effect may be related to dysregulation of 5-HT function in orbitofrontal cortex, as a model of cognitive dysfunction in depression. To test the ability of chronic antidepressant drug treatment to reverse the cognitive deficit induced by CIC, it was first necessary to assess the temporal characteristics of the CIC-induced cognitive deficit. Thus, in the first study, we assessed the duration of the cognitive deficit following 2-weeks CIC stress. Replicating previous experiments, CIC induced a reversal learning deficit tested 3 days after the last cold exposure. However, cognitive performance of CIC-stressed rats was no different from unstressed controls when tested 7, 14 or 21 days after termination of the stress treatment. We next compared behavior 3 days after 2-weeks CIC to that seen 3 days after 5-weeks CIC, and found similar deficits in reversal learning. Thus, in the final study, antidepressant drug treatment was initiated after 2-weeks of CIC stress, and was maintained for 3 weeks, concurrent with the continuation of CIC stress. Both chronic and acute treatment with the selective serotonin reuptake inhibitor, citalopram, but not the norepinephrine reuptake blocker, desipramine, reversed the cognitive deficit induced by CIC stress. Thus, this stress-induced cognitive deficit may be a useful model for cognitive deficits related to prefrontal cortical hypoactivity in depression, and for investigating neurobiological mechanisms underlying the beneficial effects of chronic antidepressant drug treatment.