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雄性和雌性大鼠新生期腹侧海马损伤:对成年后水迷宫、运动活动、十字迷宫及前额叶皮质γ-氨基丁酸和谷氨酸释放的影响

Neonatal ventral hippocampal lesions in male and female rats: effects on water maze, locomotor activity, plus-maze and prefrontal cortical GABA and glutamate release in adulthood.

作者信息

Beninger Richard J, Tuerke Katharine J, Forsyth Jennifer K, Giles Andrew, Xue Lihua, Boegman Roland J, Jhamandas Khem

机构信息

Department of Psychology, Queen's University, 62 Arch Street, Kingston, ON K7L 3N6, Canada.

出版信息

Behav Brain Res. 2009 Sep 14;202(2):198-209. doi: 10.1016/j.bbr.2009.03.044. Epub 2009 Apr 11.

Abstract

Schizophrenia is characterized by diverse behavioural and neurochemical abnormalities that may be differentially expressed in males and females. Male rats with neonatal ventral hippocampal lesions (nVHL) have commonly demonstrated behavioural and neurochemical abnormalities similar to those in schizophrenia. Fewer studies have used female rats. We investigated the hypothesis that male and female nVHL rats will demonstrate behavioural abnormalities accompanied by decreased GABA and l-glutamate release in the prefrontal cortex (PFC). On postnatal day (P) 7 rats received VH injections of ibotenate (3.0 microg/0.3 microl/side; n=18) or saline (n=21) or no injections (n=22). On P56, rats began water-maze, locomotor activity and elevated plus maze testing, and were then sacrificed for potassium-evoked GABA and l-glutamate release from PFC slices. nVHL rats showed impaired performance in water maze acquisition and match-to-sample tasks, increased spontaneous and amphetamine-induced locomotor activity and increased percent open-arm time. These behavioural changes were similar in males and females. These effects were accompanied by significantly reduced potassium-evoked l-glutamate release in male and female nVHL rats relative to controls, and non-significantly lower GABA release. Findings support the notion that behavioural abnormalities in post-pubertal male and female nVHL rats are associated with decreases in PFC neurotransmitter release.

摘要

精神分裂症的特征是多样的行为和神经化学异常,这些异常在男性和女性中可能有不同的表现。患有新生儿腹侧海马损伤(nVHL)的雄性大鼠通常表现出与精神分裂症患者相似的行为和神经化学异常。使用雌性大鼠的研究较少。我们研究了这样一个假设,即雄性和雌性nVHL大鼠会表现出行为异常,同时前额叶皮质(PFC)中的γ-氨基丁酸(GABA)和L-谷氨酸释放减少。在出生后第7天,给大鼠在腹侧海马注射鹅膏蕈氨酸(3.0微克/0.3微升/侧;n = 18)、生理盐水(n = 21)或不注射(n = 22)。在出生后第56天,大鼠开始进行水迷宫、运动活动和高架十字迷宫测试,然后处死以检测PFC切片中钾离子诱发的GABA和L-谷氨酸释放。nVHL大鼠在水迷宫获取和匹配样本任务中的表现受损,自发活动和苯丙胺诱导的运动活动增加,开放臂时间百分比增加。这些行为变化在雄性和雌性中相似。与对照组相比,这些效应伴随着雄性和雌性nVHL大鼠中钾离子诱发的L-谷氨酸释放显著减少,而GABA释放则有非显著性降低。研究结果支持这样一种观点,即青春期后雄性和雌性nVHL大鼠的行为异常与PFC神经递质释放减少有关。

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