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应激和再应激增强大鼠的条件性味觉厌恶学习:额叶皮质和海马毒蕈碱受体可能参与其中。

Stress and re-stress increases conditioned taste aversion learning in rats: possible frontal cortical and hippocampal muscarinic receptor involvement.

作者信息

Brand Linda, Groenewald Ilse, Stein Dan J, Wegener Gregers, Harvey Brian H

机构信息

Unit for Drug Research and Development, School of Pharmacy (Pharmacology), North-West University (Potchefstroom Campus), Potchefstroom, 2520, South Africa.

出版信息

Eur J Pharmacol. 2008 May 31;586(1-3):205-11. doi: 10.1016/j.ejphar.2008.03.004. Epub 2008 Mar 13.

Abstract

Symptoms of posttraumatic stress disorder are often precipitated by sensory cues in the form of visual, auditory, olfactory and gustatory "flashbacks" resulting in enhanced fear-memory consolidation and the characteristic symptoms of re-experiencing, avoidance and hyper-arousal. Single prolonged stress with and without re-stress have been used to explore the neurobiology of this disorder, particularly with respect to contextual conditioning and spatial memory impairment. However, less work has been done regarding associative sensory-related memories linked to aversive events. Although growing evidence supports a role for cholinergic pathways in stress, this has not been studied in the above animal models. We studied the effects of single prolonged stress with and without re-stress on conditioned taste aversion learning in rats, together with differential analysis of frontal cortical and hippocampal [3H]-quinuclidinyl benzylate ([3H]-QNB) muscarinic receptor binding. Single prolonged stress with and without re-stress both enhanced associative sensory aversion learning 7 days after stressor-taste pairing, although re-stress did not strengthen this response. Increased cortical and hippocampal muscarinic receptor density (Bmax) was found 7 days after single prolonged stress with re-stress, although receptor affinity remained unaltered. Frontal cortical and hippocampal muscarinic receptor changes may thus underlie conditioned taste aversion learning in rats exposed to stress and re-stress. These data suggest that it may be useful to study the role of cholinergic pathways in mediating associative memory in psychiatric disorders such as posttraumatic stress disorder.

摘要

创伤后应激障碍的症状通常由视觉、听觉、嗅觉和味觉“闪回”形式的感觉线索引发,导致恐惧记忆巩固增强以及再次体验、回避和过度觉醒的典型症状。有无再次应激的单次长时间应激已被用于探索该障碍的神经生物学,特别是关于情境条件作用和空间记忆损害方面。然而,关于与厌恶事件相关的联想性感觉相关记忆的研究较少。尽管越来越多的证据支持胆碱能通路在应激中起作用,但在上述动物模型中尚未对此进行研究。我们研究了有无再次应激的单次长时间应激对大鼠条件性味觉厌恶学习的影响,以及额叶皮质和海马体[3H] - 喹核醇基苯甲酸酯([3H] - QNB)毒蕈碱受体结合的差异分析。尽管再次应激并未增强这种反应,但有无再次应激的单次长时间应激在应激源 - 味觉配对7天后均增强了联想性感觉厌恶学习。在有再次应激的单次长时间应激7天后,发现皮质和海马体毒蕈碱受体密度(Bmax)增加,尽管受体亲和力保持不变。因此,额叶皮质和海马体毒蕈碱受体的变化可能是暴露于应激和再次应激的大鼠条件性味觉厌恶学习的基础。这些数据表明,研究胆碱能通路在介导诸如创伤后应激障碍等精神疾病中的联想记忆方面的作用可能是有用的。

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