Chronic intermittent cold stress and serotonin depletion induce deficits of reversal learning in an attentional set-shifting test in rats
Chronic intermittent cold stress and serotonin depletion induce deficits of reversal learning in an attentional set-shifting test in rats
复制标题
DOI：
10.1007/s00213-008-1224-6
复制
发表时间：
2009-01-01
影响因子：
3.4
通讯作者：
Morilak, David A.
中科院分区：
文献类型：
--
作者：
Lapiz-Bluhm, M. Danet S.;Soto-Pina, Alexandra E.;Morilak, David A.
Chronic stress perturbs modulatory brain neurotransmitter systems, including serotonin (5-HT), and is a risk factor for psychiatric disorders such as depression. Deficits in cognitive flexibility, reflecting prefrontal cortical dysfunction, are prominent in such disorders. Orbitofrontal cortex (OFC) has been implicated specifically in reversal learning, a form of cognitive flexibility modulated by 5-HT.The objectives of the study were (1) to assess the effects of chronic intermittent cold (CIC) stress, a potent metabolic stressor, on performance of rats in an attentional set-shifting test (AST), and (2) to assess a possible role for serotonin in CIC-induced deficits and test the effects of acute serotonin reuptake blockade.Male Sprague-Dawley rats were exposed to CIC stress (14 days x 6 h/day at 4A degrees C) before testing on the AST. In subsequent experiments, brain 5-HT was depleted in na < ve rats with para-chlorophenylalanine or 5-HT release was increased acutely in CIC-stressed rats with citalopram (5 mg/kg, s.c.) given 30 min prior to the first reversal task. Microdialysis was used to assess CIC-induced changes in 5-HT release in OFC during testing.CIC-stressed rats exhibited a selective impairment on the first reversal task in the AST. 5-HT depletion induced a similarly selective deficit in reversal learning. The CIC-induced impairment in reversal learning was attenuated by acute 5-HT reuptake blockade. 5-HT release was reduced in OFC of CIC-stressed rats during behavioral testing.The CIC stress-induced impairment of cognitive flexibility may involve dysregulation of 5-HT modulatory function in OFC. Such deficits may thus model relevant symptoms of neuropsychiatric disorders that respond positively to SSRI treatment.
