Schwabe Kerstin, Enkel Thomas, Klein Steffen, Schütte Michael, Koch Michael
Brain Research Institute, Department of Neuropharmacology, University of Bremen, FB2 P.O. Box 330440, 28334 Bremen, Germany.
Behav Brain Res. 2004 Aug 12;153(1):21-34. doi: 10.1016/j.bbr.2003.10.030.
While prefrontal lesions in rodents serve as models for frontal lobe syndromes, neonatal lesions are considered as models for disconnection syndromes, such as schizophrenia. We investigated the effect of neonatal lesions of the rat medial prefrontal cortex (mPFC) together with pubertal dexamethasone-challenge on adult rat behaviour and on apomorphine-induced behavioural changes. Adult lesions were used as controls. Rats with neonatal (postnatal day 7) or adult excitotoxic lesions or sham-lesions of the mPFC were tested 9 weeks after surgery. At postnatal day 49 one group of neonatal operated rats were systemically injected with the glucocorticoid receptor agonist dexamethasone (20 mg/kg), in order to simulate stress-induced glucocorticoid receptor activation. Working memory and perseveration was tested in T-maze tasks (continuous delayed alternation and reversal learning). Additionally, locomotor activity and prepulse inhibition (PPI) of startle was tested with and without apomorphine-treatment. Brain tissue damage was assessed using Nissl-staining and parvalbumine-immunocytochemistry. Pronounced thinning of the prelimbic-infralimbic subregion of the mPFC accompanied by altered cytoarchitecture and reduced number of parvalbumine-immunopositive neurones was found after neonatal lesions while adult lesions resulted in loss of neurones accompanied by gliosis. Neonatal lesions increased perseveration in the T-maze tasks and enhanced PPI, while adult lesions induced a working memory deficit. This differential behavioural outcome presumably reflects neurodevelopmentally induced alterations in neuronal circuits after neonatal lesions versus damage to mPFC alone after adult lesions. Dexamethasone-injection at day 49 did not alter behaviour in these tasks. Motor activity was not affected by neonatal or adult lesions but dexamethasone reduced apomorphine-induced hyperlocomotion.
虽然啮齿动物的前额叶损伤可作为额叶综合征的模型，但新生期损伤被视为诸如精神分裂症等分离综合征的模型。我们研究了新生大鼠内侧前额叶皮质（mPFC）损伤以及青春期地塞米松激发对成年大鼠行为和阿扑吗啡诱导的行为变化的影响。以成年期损伤作为对照。对在出生后第7天接受新生期或成年期兴奋性毒性损伤或mPFC假损伤的大鼠在手术后9周进行测试。在出生后第49天，对一组接受新生期手术的大鼠全身注射糖皮质激素受体激动剂地塞米松（20 mg/kg），以模拟应激诱导的糖皮质激素受体激活。在T迷宫任务（连续延迟交替和逆向学习）中测试工作记忆和持续性。此外，在有或没有阿扑吗啡处理的情况下测试运动活动和惊吓前脉冲抑制（PPI）。使用尼氏染色和小白蛋白免疫细胞化学评估脑组织损伤。新生期损伤后发现mPFC的前边缘-下边缘亚区明显变薄，伴有细胞结构改变和小白蛋白免疫阳性神经元数量减少，而成年期损伤导致神经元丢失并伴有胶质增生。新生期损伤增加了T迷宫任务中的持续性并增强了PPI，而成年期损伤诱导了工作记忆缺陷。这种不同的行为结果可能反映了新生期损伤后神经发育诱导的神经回路改变与成年期损伤后仅mPFC受损的情况。在第49天注射地塞米松并未改变这些任务中的行为。运动活动不受新生期或成年期损伤的影响，但地塞米松减少了阿扑吗啡诱导的运动亢进。
