Behavioural and neurochemical features of olfactory bulbectomized rats resembling depression with comorbid anxiety
Behavioural and neurochemical features of olfactory bulbectomized rats resembling depression with comorbid anxiety
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DOI：
10.1016/j.bbr.2007.01.003
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发表时间：
2007-03-28
影响因子：
2.7
通讯作者：
Nabeshima, Toshitaka
中科院分区：
文献类型：
--
作者：
Wang, Dayong;Noda, Yukihiro;Nabeshima, Toshitaka
为了探讨嗅球切除（013）大鼠作为抑郁症模型的性质和有效性，我们重新评估了与抑郁症症状和神经化学异常相关的行为和神经化学缺陷，使用我们的方案，其中区分性行为测试中的快感缺乏样行为，海马（Hip）依赖的长期记忆和焦虑样行为。除了探索性多动反应的一种新的环境压力类似的精神激动，OB大鼠表现出性欲下降，和赤字的长期外显记忆，类似于抑郁症患者的兴趣和认知缺陷的损失，分别。013大鼠在社会交往和十字迷宫实验中也表现出类似焦虑的行为。在OB大鼠中，我们发现梨状皮质神经元变性，前额叶皮质（PFC）、Hip和杏仁核（Amg）中NMDA受体亚单位1（NR 1）蛋白表达降低，但NR 2A或NR 2B蛋白表达不变，PFC和Hip中cAMP反应元件结合蛋白（CREB）磷酸化水平降低，但Amg无变化。OB大鼠的行为和神经化学异常，除了在十字迷宫任务和神经元变性的性能，显着衰减地昔帕明（10毫克/公斤），一种典型的抗抑郁药重复治疗。本研究提示，OB大鼠可能是一种焦虑共病的抑郁模型，表现为激越、性功能和认知功能障碍、神经元变性、NR 1蛋白表达降低。减少CREB的磷酸化。(c)2007 Elsevier B. V.保留所有权利。
In order to probe the nature and validity of olfactory bulbectomized (013) rats as a model of depression, we reevaluated their behavioural and neurochemical deficits in relation to the symptoms and neurochemical abnormalities of depression using our protocols, which distinguish anhedonia-resembling behaviour in sexual behavioural test, the hippocampus (Hip)-dependent long-term memory and anxiety-resembling behaviour specially. Besides exploratory hyperactivity in response to a novel environmental stress resembling the psychomotor agitation, OB rats showed a decrease of libido, and a deficit of long-term explicit memory, resembling loss of interest and cognitive deficits in depressive patients, respectively. 013 rats also exhibited the anxiety symptom-resembling behaviour in social interaction and plus-maze tests. In the OB rats, we found degenerated neurons in the piriform cortex, decreased protein expression of NMDA receptor subunit 1 (NR1), but not NR2A or NR2B, in the prefrontal cortex (PFC), Hip and amygdala (Amg), and decreased phosphorylation of cAMP-response element-binding protein (CREB) in the PFC and Hip, but not Amg. The behavioural and neurochemical abnormalities in OB rats, except for the performance in the plus-maze task and neuronal degeneration, were significantly attenuated by repeated treatment with desipramine ( 10 mg/kg), a typical antidepressant. The present study indicated that OB rats may be a model of depression with comorbid anxiety, characterized by agitation, sexual and cognitive dysfunction, neuronal degeneration, decreased protein expression of NR1. and decreased phosphorylation of CREB. (c) 2007 Elsevier B.V. All rights reserved.