Luyten L, Schroyens N, Luyck K, Fanselow M S, Beckers T
Research Group Psychology of Learning and Experimental Psychopathology, Faculty of Psychology and Educational Sciences, KU Leuven, Leuven, Belgium.
Research Group Experimental Neurosurgery and Neuroanatomy, KU Leuven, Leuven, Belgium.
Transl Psychiatry. 2016 Sep 27;6(9):e903. doi: 10.1038/tp.2016.183.
The excessive transfer of fear acquired for one particular context to similar situations has been implicated in the development and maintenance of anxiety disorders, such as post-traumatic stress disorder. Recent evidence suggests that glucose ingestion improves the retention of context conditioning. It has been speculated that glucose might exert that effect by ameliorating hippocampal functioning, and may hold promise as a therapeutic add-on in traumatized patients because improved retention of contextual fear could help to restrict its generalization. However, direct data regarding the effect of glucose on contextual generalization are lacking. Here, we introduce a new behavioral protocol to study such contextual fear generalization in rats. In adult Wistar rats, our procedure yields a gradient of generalization, with progressively less freezing when going from the original training context, over a perceptually similar generalization context, to a markedly dissimilar context. Moreover, we find a flattening of the gradient when the training-test interval is prolonged with 1 week. We next examine the effect of systemic glucose administration on contextual generalization with this novel procedure. Our data do not sustain generalization-reducing effects of glucose and question its applicability in traumatic situations. In summary, we have developed a replicable contextual generalization procedure for rats and demonstrate how it is a valuable tool to examine the neurobiological correlates and test pharmacological interventions pertaining to an important mechanism in the etiology of pathological anxiety.
因某一特定情境而产生的恐惧过度转移至类似情境，这与焦虑症（如创伤后应激障碍）的发生和维持有关。最近的证据表明，摄入葡萄糖可改善情境条件反射的记忆保持。据推测，葡萄糖可能通过改善海马功能发挥这种作用，并且可能有望作为创伤患者的一种辅助治疗手段，因为改善情境恐惧的记忆保持有助于限制其泛化。然而，关于葡萄糖对情境泛化影响的直接数据尚缺。在此，我们引入一种新的行为学方案来研究大鼠的这种情境恐惧泛化。在成年Wistar大鼠中，我们的程序产生了一种泛化梯度，从最初的训练情境开始，经过感知上相似的泛化情境，到明显不同的情境，冻结反应逐渐减少。此外，我们发现当训练 - 测试间隔延长1周时，梯度会变平缓。接下来，我们用这种新程序研究全身给予葡萄糖对情境泛化的影响。我们的数据不支持葡萄糖具有减少泛化的作用，并对其在创伤情境中的适用性提出质疑。总之，我们为大鼠开发了一种可重复的情境泛化程序，并证明它是一种有价值的工具，可用于研究与病理性焦虑病因中一种重要机制相关的神经生物学关联并测试药物干预。
