Department of Neuroscience & Pharmacology, Rudolf Magnus Institute, University Medical Centre Utrecht, The Netherlands.
Neuropharmacology. 2013 Jul;70:306-15. doi: 10.1016/j.neuropharm.2013.02.008. Epub 2013 Mar 5.
Corticosteroid hormones, released after stress, are known to change neuronal activity in two time-domains: within minutes via non-genomic pathways and with a delay of >1 h through pathways involving transcriptional regulation. Recent evidence in rodents and humans indicates that these two modes of corticosteroid action differently affect cognitive tasks. Here, we investigated whether reward-based decision-making, in a rat model of the Iowa Gambling Task (rIGT), is also differently altered by rapid versus delayed actions of corticosterone. We targeted the rapid and delayed time domain by injecting corticosterone (CORT, 1 mg/kg, s.c.) at 30 min (rapid) or 180 min (delayed) respectively prior to behavioural testing, during the final 3 days of the behavioural paradigm. In saline treated rats, the number of visits to the disadvantageous arm decreased over trial blocks, whilst this was attenuated when CORT was administered 30 min before testing. This attenuation was associated with a significantly increased c-Fos expression in the lateral orbitofrontal cortex and insular cortex, and a trend for an increase in the infralimbic cortex. The rapid corticosteroid effect contrasted with treatment 180 min before testing, where the number of visits to the disadvantageous arm as well as c-Fos labelling was not affected. These findings indicate that rapid corticosteroid actions impair reward-based decision-making.
皮质甾类激素在应激后释放,已知其可通过两种时相来改变神经元活动:通过非基因途径在数分钟内,以及通过涉及转录调节的途径延迟 >1 小时。最近在啮齿动物和人类中的证据表明,皮质甾类的这两种作用模式以不同的方式影响认知任务。在这里,我们研究了基于奖励的决策(在大鼠的爱荷华赌博任务(rIGT)模型中)是否也因皮质酮的快速与延迟作用而发生不同改变。我们通过在行为测试前分别在 30 分钟(快速)或 180 分钟(延迟)时注射皮质酮(CORT,1 mg/kg,sc)来靶向快速和延迟时间域,在行为范式的最后 3 天内进行。在生理盐水处理的大鼠中,随着试验块的进行,不利臂的访问次数减少,而当 CORT 在测试前 30 分钟给予时,这种减少被减弱。这种减弱与外侧眶额皮质和岛叶皮质中 c-Fos 表达的显著增加以及在边缘下皮质中增加的趋势相关。快速的皮质酮作用与在测试前 180 分钟的治疗作用形成对比,在这种情况下,不利臂的访问次数和 c-Fos 标记均不受影响。这些发现表明,快速的皮质酮作用会损害基于奖励的决策。