Jones Nigel C, Kumar Gaurav, O'Brien Terence J, Morris Margaret J, Rees Sandra M, Salzberg Michael R
Department of Medicine, University of Melbourne, 4th Floor Clinical Sciences Building, Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3052, Australia.
Behav Brain Res. 2009 Oct 12;203(1):81-7. doi: 10.1016/j.bbr.2009.04.023. Epub 2009 May 3.
The incidence of psychiatric disturbances is elevated in temporal lobe epilepsy (TLE) patients. Early life stressful events are believed to have a major impact on mental health later in life, and increasing evidence suggests that such stresses may also promote a vulnerability to TLE. This study investigated whether subjecting rats to early life stress exacerbated mood and cognitive disturbances associated with the development of epilepsy. On postnatal days 2-14, rat pups were separated from their dams for either 180 min/day (handling and maternal separation--HMS180, modelling early life stress) or 15 min/day (control handling and maternal separation--HMS15). At 7 weeks, rats were implanted with a bipolar electrode into the left amygdala. Following recovery, one group of rats from each litter underwent rapid amygdala kindling (RAK) epileptogenesis, while another underwent sham kindling. One week following this, rats were subjected to behavioural tests assessing anxiety and cognition. HMS180-exposed rats kindled faster than HMS15 rats (p<0.0001). RAK induced a potent anxiolytic effect as evidenced by increased % time spent in the open arms of the elevated plus maze, compared with sham kindled rats (p<0.0001). This anxiolytic effect was also observed in the open field task, as evidenced by increased time spent in the inner area (p=0.010). Neither RAK nor maternal separation had any effect on cognitive function in the Morris water maze. We conclude that maternal separation stress accelerates limbic epileptogenesis in adult rats, and that RAK induces potent anxiolytic effects that are not influenced by such early life stressful events.
颞叶癫痫（TLE）患者中精神障碍的发生率升高。早年的应激事件被认为会对晚年的心理健康产生重大影响，越来越多的证据表明，此类应激也可能增加患TLE的易感性。本研究调查了使大鼠经历早年应激是否会加剧与癫痫发展相关的情绪和认知障碍。在出生后第2 - 14天，将幼鼠与其母鼠分离，每天分离180分钟（处理和母鼠分离——HMS180，模拟早年应激）或每天分离15分钟（对照处理和母鼠分离——HMS15）。7周时，将双极电极植入大鼠左侧杏仁核。恢复后，每窝中的一组大鼠进行快速杏仁核点燃（RAK）致痫，另一组进行假点燃。在此之后一周，对大鼠进行评估焦虑和认知的行为测试。经历HMS180的大鼠比经历HMS15的大鼠点燃速度更快（p<0.0001）。与假点燃大鼠相比，RAK诱导了显著的抗焦虑作用，高架十字迷宫开放臂停留时间百分比增加证明了这一点（p<0.0001）。在旷场试验中也观察到了这种抗焦虑作用，内侧区域停留时间增加证明了这一点（p = 0.010）。RAK和母鼠分离对Morris水迷宫中的认知功能均无影响。我们得出结论，母鼠分离应激会加速成年大鼠边缘叶癫痫的发生，并且RAK诱导的显著抗焦虑作用不受此类早年应激事件的影响。
