Segovia Gregorio, Del Arco Alberto, de Blas Marta, Garrido Pedro, Mora Francisco
Department of Physiology, Faculty of Medicine, Universidad Complutense, Ciudad Universitaria, s/n, 28040 Madrid, Spain.
Behav Brain Res. 2008 Mar 5;187(2):304-11. doi: 10.1016/j.bbr.2007.09.024. Epub 2007 Sep 25.
The present study was designed to investigate the effects of a mild acute stress on the in vivo release of dopamine in the prefrontal cortex (PFC) during aging and whether housing animals in an enriched environment changes these effects. Behavioural parameters such as spontaneous motor activity (open-field) and working memory performance in a delayed alternation task (water T-maze) were also studied. Male Wistar rats (3 months of age) were housed during 3, 12, and 21 months (6, 15 and 24 months of age at the end of housing) in enriched or control conditions. After behavioural testing, animals were subdivided in two groups. In one of the groups BDNF protein levels were determined in PFC, hippocampus and amygdala. Rats of the second group were implanted with guide cannula in the PFC to perform microdialysis experiments and to monitor extracellular concentrations of dopamine. The release of dopamine in the PFC produced by handling stress (40 min) was significantly reduced in both enriched and control 24 months animals. However, the increases of dopamine produced by stress were significantly lower in enriched animals when compared to controls. Similarly, the increases of dopamine produced by perfusing K(+) 100 mM into the PFC were also reduced by aging and environmental enrichment. Both spontaneous motor activity and working memory performance were significantly reduced by aging. Moreover, animals housed in an enriched environment did show a lower spontaneous motor activity at all ages studied, though they did not show any change in performing the working memory task, either in basal conditions or after an acute stress. The BDNF protein levels were increased by environmental enrichment in the hippocampus and amygdala, but not in the PFC. These results suggest that both environmental enrichment and aging reduces the activity of the mesocortical dopamine system.
本研究旨在调查轻度急性应激对衰老过程中前额叶皮质(PFC)内多巴胺体内释放的影响,以及将动物饲养在丰富环境中是否会改变这些影响。还研究了行为参数,如自发运动活动(旷场试验)和延迟交替任务(水迷宫)中的工作记忆表现。雄性Wistar大鼠(3月龄)在3个月、12个月和21个月(饲养结束时分别为6个月、15个月和24个月龄)期间饲养在丰富环境或对照条件下。行为测试后,将动物分为两组。一组测定PFC、海马体和杏仁核中的BDNF蛋白水平。第二组大鼠在PFC植入引导套管,以进行微透析实验并监测多巴胺的细胞外浓度。在丰富环境和对照环境中饲养24个月的动物,由处理应激(40分钟)引起的PFC中多巴胺释放均显著降低。然而,与对照组相比,丰富环境中的动物应激引起的多巴胺增加显著更低。同样,向PFC灌注100 mM K(+) 引起的多巴胺增加也因衰老和环境丰富而减少。自发运动活动和工作记忆表现均因衰老而显著降低。此外,饲养在丰富环境中的动物在所有研究年龄组中自发运动活动均较低,尽管它们在基础条件下或急性应激后执行工作记忆任务时未表现出任何变化。环境丰富使海马体和杏仁核中的BDNF蛋白水平升高,但PFC中未升高。这些结果表明,环境丰富和衰老均会降低中皮质多巴胺系统的活性。