Ambiguous-Cue Interpretation is Biased Under Stress- and Depression-Like States in Rats
Ambiguous-Cue Interpretation is Biased Under Stress- and Depression-Like States in Rats
复制标题
DOI：
10.1038/npp.2009.204
复制
发表时间：
2010-03-01
影响因子：
7.6
通讯作者：
Vollmayr, Barbara
中科院分区：
文献类型：
--
作者：
Enkel, Thomas;Gholizadeh, Donya;Vollmayr, Barbara
负面认知偏差--倾向于悲观地解读模棱两可的情况--是抑郁症等压力相关障碍的核心特征。然而，这种偏见的神经生物学基础仍然不清楚，尤其是因为缺乏翻译工具。我们建立了一个新的模糊线索解释范式，并就抑郁症的病因，评估了环境和遗传因素是否导致了负面偏见。训练大鼠按下杠杆，以获得食物奖励，根据一个音调，并根据不同的音调按下另一个杠杆，以避免受到电击脚的惩罚。在模糊线索测验中，对频率在训练音调中间的音调的杠杆按压反应被作为大鼠对积极或消极事件的预期的指标。在抑郁症的遗传性动物模型--先天性无助大鼠中，由于阳性反应减少和阴性反应增加而导致的负反应偏向被发现。此外，用去甲肾上腺素-糖皮质激素联合治疗，模拟内源性神经调节中与应激相关的变化，使大鼠远离阳性反应。这种反应转变伴随着齿状回和杏仁核神经元的激活。因此，抑郁症的环境和遗传风险因素会导致反应偏差，这类似于抑郁症患者的悲观偏差。所描述的行为范式构成了研究模糊条件下决策的神经元基础的有用工具，并可能促进抑郁症的创新药物治疗和心理治疗。神经精神药理学(2010年)35,1008-1015；DOI：10.1038/npp.2009.204；2009年12月30日在线发布
Negative cognitive bias-the tendency to interpret ambiguous situations pessimistically-is a central feature of stress-related disorders such as depression. The underlying neurobiology of this bias, however, remains unclear, not least because of a lack of translational tools. We established a new ambiguous-cue interpretation paradigm and, with respect to the etiology of depression, evaluated if environmental and genetic factors contribute to a negative bias. Rats were trained to press a lever to receive a food reward contingent to one tone and to press another lever in response to a different tone to avoid punishment by electric foot-shock. In the ambiguous-cue test, the lever-press responses to tones with frequencies intermediate to the trained tones were taken as indicators for the rats' expectation of a positive or negative event. A negative response bias because of decreased positive and increased negative responding was found in congenitally helpless rats, a genetic animal model of depression. Moreover, treatment with a combined noradrenergic-glucocorticoid challenge, mimicking stress-related changes in endogenous neuromodulation, biased rats away from positive responding. This response shift was accompanied by neuronal activation in dentate gyrus and amygdala. Thus, environmental and genetic risk factors for depression induce a response bias, which resembles the pessimistic bias of patients suffering from depression. The behavioral paradigm described constitutes a useful tool to study the neuronal basis of decision making under ambiguous conditions and may promote innovative pharmaco- and psychotherapy for depression. Neuropsychopharmacology (2010) 35, 1008-1015; doi:10.1038/npp.2009.204; published online 30 December 2009