A cognitive deficit induced in rats by chronic intermittent cold stress is reversed by chronic antidepressant treatment

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Abstract
We have previously reported that 14-d 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 experiment, we assessed the duration of the cognitive deficit following 2-wk CIC stress. Replicating previous experiments, CIC induced a reversal learning deficit tested 3 d after the last cold exposure. However, cognitive performance of CIC-stressed rats was no different from unstressed controls when tested 7, 14 or 21 d after termination of the stress treatment. We next compared behaviour 3 d after 2-wk CIC to that seen 3 d after 5-wk CIC, and found similar deficits in reversal learning. Thus, in the final experiment, antidepressant drug treatment was initiated after 2-wk CIC stress, and was maintained for 3 wk, 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.