Ho Ying-Jui, Hsu Li-Sung, Wang Ching-Fu, Hsu Wen-Yu, Lai Te-Jen, Hsu Cheng-Chin, Tsai Yuan-Feen
Division of Clinical Psychology, School of Psychology, Chung Shan Medical University, Tai-Chung City 402, Taiwan, ROC.
Brain Res. 2005 May 10;1043(1-2):179-85. doi: 10.1016/j.brainres.2005.02.057.
It has been reported that the glutamatergic N-methyl-D-aspartate (NMDA) receptor is involved in stress responses and that anxiety is the primary response to stress. Although individual differences in anxiety levels of rats have been demonstrated by using the elevated plus-maze (PM) test, the role of NMDA receptor activity in such individuality of anxiety is not clear. Here, we examined whether low (LA) and high (HA) anxiety rats might respond differently to treatment with d-cycloserine (DCS), a partial agonist of the glycine binding site located on NMDA receptors. Male Wistar rats were screened by using the PM and divided into LA and HA subgroups. On the next day, these rats were again tested in the PM, 30 min after the treatment with DCS (5, 10, or 30 mg/kg ip). Five days later, the rats were subjected to a 2-day forced swim (FS) test, receiving the DCS treatment again 30 min before the second day session. The PM data showed that DCS had anxiogenic effects in LA but not HA rats. The immobility of LA or HA rats in the FS test was not affected by DCS. The results indicate that the behavioral effects of DCS depend on the anxiety level of rats and have task-dependent behavioral consequences, suggesting that glycine binding sites on NMDA receptors are involved in individual differences of anxiety level.
据报道，谷氨酸能N-甲基-D-天冬氨酸（NMDA）受体参与应激反应，且焦虑是应激的主要反应。尽管通过高架十字迷宫（EPM）试验已证明大鼠焦虑水平存在个体差异，但NMDA受体活性在这种焦虑个体差异中的作用尚不清楚。在此，我们研究了低焦虑（LA）和高焦虑（HA）大鼠对d-环丝氨酸（DCS）治疗的反应是否不同，DCS是位于NMDA受体上甘氨酸结合位点的部分激动剂。通过EPM筛选雄性Wistar大鼠，并将其分为LA和HA亚组。第二天，这些大鼠在腹腔注射DCS（5、10或30mg/kg）30分钟后，再次进行EPM试验。五天后，大鼠接受为期2天的强迫游泳（FS）试验，在第二天试验前30分钟再次接受DCS治疗。EPM数据显示，DCS对LA大鼠有促焦虑作用，而对HA大鼠没有。DCS不影响LA或HA大鼠在FS试验中的不动时间。结果表明，DCS的行为效应取决于大鼠的焦虑水平，并具有任务依赖性的行为后果，提示NMDA受体上的甘氨酸结合位点参与了焦虑水平的个体差异。
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