IMPAIRED SOCIAL INTERACTION AND ENHANCED SENSITIVITY TO PHENCYCLIDINE-INDUCED DEFICITS IN NOVEL OBJECT RECOGNITION IN RATS WITH CORTICAL CHOLINERGIC DENERVATION
IMPAIRED SOCIAL INTERACTION AND ENHANCED SENSITIVITY TO PHENCYCLIDINE-INDUCED DEFICITS IN NOVEL OBJECT RECOGNITION IN RATS WITH CORTICAL CHOLINERGIC DENERVATION
复制标题
DOI：
10.1016/j.neuroscience.2011.08.027
复制
发表时间：
2011-11-10
期刊：
影响因子：
3.3
通讯作者：
Mattsson, A.
中科院分区：
文献类型：
--
作者：
Savage, S.;Kehr, J.;Mattsson, A.
胆碱能神经传递失调与精神分裂症的病理生理学有关，特别是阴性症状和认知缺陷。本研究的目的是评估新皮层胆碱能神经支配和N-甲基-D-天冬氨酸（NMDA）受体拮抗剂苯环利定（PCP）对社会互动和新物体识别（NOR），陈述性记忆任务的作用。胆碱能皮质脑投射损伤的免疫毒素192 IgG-皂草素局部灌注到成年雄性李斯特帽大鼠的基底核大细胞。2.5周后，在社交互动范式中评估行为，然后进行NOR任务。我们发现，选择性的胆碱能神经去支配新皮层导致社会互动的持续时间显着减少，特别是积极的社会互动。急性服用五氯苯酚（1.0毫克/千克，皮下注射）导致活跃的社会互动显著减少，使得完整和去神经动物之间不再有区别。无论是单独的胆碱能去神经，还是PCP（1.0 mg/kg，s.c.）单独使用会阻碍老鼠识别新物体的能力。然而，当缺乏皮质胆碱能神经支配的动物受到PCP的挑战时，它们不再能够识别新的物体。这项研究表明，大鼠缺乏胆碱能神经支配的新皮层受损的社会互动，特别是积极接触的时间缩短。具有严重皮质胆碱能功能减退的动物保持在陈述性记忆测试中执行的能力，尽管任务执行的强度较低。然而，在正常动物中，PCP本身不会损害表现的剂量对精神病样行为的激发，将消除缺乏皮质胆碱能神经支配的动物识别新物体的能力。本研究结果支持皮质胆碱能功能减退在精神分裂症的阴性和认知症状中的可能作用，以及胆碱能增强作为抗精神病药物药理学特征的一部分的潜力。(C)2011年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Dysregulated cholinergic neurotransmission has been implicated in the pathophysiology of schizophrenia, particularly negative symptoms and cognitive deficits. The aim of the present study was to evaluate the role of neocortical cholinergic innervation and of the N-methyl-D-aspartate (NMDA) receptor antagonist phencyclidine (PCP) on social interaction and novel object recognition (NOR), a declarative memory task. The cholinergic corticopetal projection was lesioned by local infusion of the immunotoxin 192 IgG-saporin into nucleus basalis magnocellularis of adult male Lister hooded rats. Behavior was assessed 2.5 weeks later in a social interaction paradigm followed by the NOR task. We found that selective cholinergic denervation of neocortex led to a significant reduction in duration of social interaction, specifically active social interaction. Acute administration of PCP (1.0 mg/kg, s.c.) caused a marked decrease of active social interaction, such that there was no longer a difference between intact and denervated animals. Neither cholinergic denervation alone, nor PCP (1.0 mg/kg, s.c.) alone blocked the ability of rats to recognize a novel object. However, when animals lacking cortical cholinergic innervation were challenged by PCP, they were no longer able to recognize a novel object. This study indicates that rats lacking cholinergic innervation of neocortex have impaired social interaction and specifically that the duration of active contact is shortened. Animals with severe cortical cholinergic hypofunction maintain the ability to perform in a declarative memory test, although the task is carried out less intensively. However, a provocation of psychosis-like behavior by a dose of PCP that does not by itself impair performance in normal animals, will abolish the ability to recognize novel objects in animals lacking cortical cholinergic innervation. The present findings support a possible role for cortical cholinergic hypofunction in the negative and cognitive symptoms of schizophrenia, and the potential for cholinergic augmentation as part of the pharmacological profile of antipsychotic drugs. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.