Pietersen Charmaine Y, Bosker Fokko J, Postema Folkert, Fokkema Dirk S, Korf Jakob, den Boer Johan A
Graduate School of Behavioural and Cognitive Neuroscience, Department of Psychiatry, University Medical Centre Groningen, University of Groningen, Groningen 9713GZ, The Netherlands.
Prog Neuropsychopharmacol Biol Psychiatry. 2006 Sep 30;30(7):1209-18. doi: 10.1016/j.pnpbp.2006.02.019. Epub 2006 Apr 19.
The neurotransmitter glutamate and its associated receptors perform an important role in the brain circuitry underlying normal fear processing. The glutamate NMDA receptor, in particular, is necessary for the acquisition and recollection of conditioned-fear responses. Here the authors examine how acute blockage of the NMDA receptor with sub-anaesthetic doses of ketamine affects behavioural assays of fear-conditioned stress (e.g. freezing) and cFos expression in a network of brain areas that have previously been implicated in fear processing. Fear-conditioned rats displayed significantly more freezing behaviour than non-conditioned controls. In fear-conditioned rats that also received ketamine, this conditioning effect was largely neutralised. Fear conditioning also led to increased cFos expression in various areas central to fear processing, including the basolateral nucleus of the amygdala, the paraventricular nucleus of the hypothalamus and the anterior cingulate. Ketamine abolished such increases in cFos expression in most brain areas investigated. The present study therefore demonstrates that systemic ketamine administration in rats interferes with fear conditioning on a behavioural level and in a network of brain regions associated with fear and anxiety. The combination of ketamine and fear conditioning may therefore provide a useful model of abnormal fear processing, as observed in certain psychiatric conditions.
神经递质谷氨酸及其相关受体在正常恐惧处理的脑回路中发挥着重要作用。尤其是谷氨酸N-甲基-D-天冬氨酸（NMDA）受体，对于条件性恐惧反应的习得和回忆是必需的。在此，作者研究了用亚麻醉剂量的氯胺酮急性阻断NMDA受体如何影响恐惧条件性应激的行为测定（如僵住）以及先前涉及恐惧处理的脑区网络中的cFos表达。与未接受条件刺激的对照组相比，接受恐惧条件刺激的大鼠表现出显著更多的僵住行为。在同时接受氯胺酮的恐惧条件刺激大鼠中，这种条件刺激效应在很大程度上被抵消。恐惧条件刺激还导致在恐惧处理核心的各个区域中cFos表达增加，包括杏仁核基底外侧核、下丘脑室旁核和前扣带回。氯胺酮消除了在所研究的大多数脑区中cFos表达的这种增加。因此，本研究表明，在大鼠中全身给予氯胺酮会在行为水平以及与恐惧和焦虑相关的脑区网络中干扰恐惧条件反射。因此，氯胺酮与恐惧条件刺激的结合可能提供一种有用的异常恐惧处理模型，如在某些精神疾病中所观察到的那样。
