Karrenbauer Britta D, Ho Ying-Jui, Ludwig Verena, Löhn Jeanette, Spanagel Rainer, Schwarting Rainer K W, Pawlak Cornelius R
Experimental and Physiological Psychology, Philipps-University, Marburg, Germany.
J Neuroimmunol. 2009 Mar 31;208(1-2):10-8. doi: 10.1016/j.jneuroim.2008.12.003. Epub 2009 Feb 8.
There is evidence that immune messengers like cytokines can modulate emotional and motivated behaviours and are involved in psychiatric conditions like anxiety, and depression. Previously, we showed that cytokine gene expression (interleukin (IL)-2 mRNA) in specific brain tissues (striatum, prefrontal cortex) correlated with anxiety-like behaviour (open arm time) in an elevated plus-maze in rats. In a subsequent experiment, a single striatal IL-2 injection showed behavioural trends with the lower dose (1 ng) acting in a behavioural suppressive way, whereas the highest dosage (25 ng) led to activation and anxiolytic-like behaviour. Here, to support and extend our previous findings, we tested Wistar outbred rats after a single unilateral (balanced brain sites) IL-2 injection into the ventral/dorsal striatum followed by an open field test acutely and 24 h later. Analyses for horizontal locomotion showed no differences between groups. However, rats with IL-2-treatment (0.1 ng) showed a dose-dependent avoidance effect (i.e. reduced centre time) compared to the 1 ng group and vehicle controls 24 h later. In addition, suppression of free rearing activity was shown for both IL-2 doses (0.1; 1 ng) compared to saline in the acute test, and partly 24 h later. Thus, in experiment 2, we tested for proactive drug mechanisms to test for delayed effects of IL-2 as observed in experiment 1. In a new sample, rats were returned to their home cages after a striatal IL-2 injection (0.1; 0.01; 0 ng), and tested 24 h and 48 h after the injection in an open field. Neither for the first (24 h) nor for the second exposure (48 h later) did the analyses show any significant behavioural effects. We therefore suggest that emotional-related behaviour can be modulated by striatal IL-2 for at least 24 h. However, such IL-2 effects can only be observed if a mild stressful environmental challenge (i.e., forced open field exposure) is followed immediately after injection. In conclusion, proactive drug effects may be excluded for striatal IL-2 effects on open field behaviour.
有证据表明，细胞因子等免疫信使可以调节情绪和动机行为，并参与焦虑和抑郁等精神疾病。此前，我们发现特定脑组织（纹状体、前额叶皮质）中的细胞因子基因表达（白细胞介素 (IL)-2 mRNA）与大鼠高架十字迷宫中的焦虑样行为（开臂时间）相关。在随后的实验中，单次纹状体注射IL-2显示出行为趋势，较低剂量（1 ng）以行为抑制方式起作用，而最高剂量（25 ng）导致激活和抗焦虑样行为。在此，为了支持和扩展我们之前的发现，我们在将单次单侧（平衡脑区）IL-2注射到腹侧/背侧纹状体后，对Wistar远交系大鼠进行了急性和24小时后的旷场试验。水平运动分析显示各组之间没有差异。然而，与1 ng组和溶剂对照组相比，接受IL-2治疗（0.1 ng）的大鼠在24小时后表现出剂量依赖性回避效应（即中心时间减少）。此外，在急性试验中，与生理盐水相比，两种IL-2剂量（0.1；1 ng）均显示出对自由站立活动的抑制作用，部分在24小时后仍有抑制作用。因此，在实验2中，我们测试了主动药物机制，以测试如实验1中观察到的IL-2的延迟效应。在一个新的样本中，大鼠在纹状体注射IL-2（0.1；0.01；0 ng）后返回其饲养笼，并在注射后24小时和48小时在旷场中进行测试。无论是第一次（24小时）还是第二次暴露（48小时后），分析均未显示任何显著的行为影响。因此，我们认为纹状体IL-2可以调节与情绪相关的行为至少24小时。然而，只有在注射后立即进行轻度应激环境挑战（即强迫旷场暴露）时，才能观察到这种IL-2效应。总之，纹状体IL-2对旷场行为的影响可能不涉及主动药物效应。
