Duncan G E, Johnson K B, Breese G R
Brain and Development Research Center, University of North Carolina at Chapel Hill 27599.
J Neurosci. 1993 Sep;13(9):3932-43. doi: 10.1523/JNEUROSCI.13-09-03932.1993.
Alterations in brain activity patterns were assessed in response to swim stress by immunocytochemical detection of Fos-like immunoreactivity (Fos-LI) and high-resolution autoradiographic imaging of 14C-2-deoxyglucose (2-DG) uptake. The stress paradigm investigated was a classic behavioral screen for antidepressant drug activity, the forced swim test. One of the most pronounced effects produced by swim stress was an increase in 2-DG uptake and induction of Fos-LI in a restricted region of the lateral septal nucleus. Specific "limbic" cortical regions, including the medial prefrontal, ventrolateral orbital, and cingulate cortices, also exhibited both increased 2-DG uptake and expression of Fos-LI in response to swim stress. In the hypothalamic paraventricular nucleus of swim-stressed rats, Fos-LI was induced but no change in 2-DG uptake was apparent. Since the specific swim stress protocol used is a behavioral screen for antidepressant drugs, the effects of imipramine on stress-induced alterations in 2-DG uptake and induction of Fos-LI were examined. The stress-induced increase in 2-DG uptake in the lateral septum was blocked by treatment with imipramine, but treatment with imipramine had no effect on induction of Fos-LI in the same region. Neither 2-DG uptake nor Fos-LI expression was altered by imipramine treatment in the cortical regions influenced by swim stress. Administration of imipramine alone under basal conditions produced a robust induction of Fos-LI in the central nucleus of the amygdala and in the dorsal lateral subdivision of the bed nucleus of the stria terminalis. No effect of imipramine treatment on 2-DG uptake was apparent in these latter regions. The results provide insights into topographic patterns of brain activity associated with swim stress and neuroanatomically selective actions of imipramine. The different and complementary information obtained by assessment of Fos-LI and 2-DG uptake illustrates the utility of applying both functional mapping approaches to examine neuroanatomical correlates of behavioral states and drug treatment.
通过免疫细胞化学检测Fos样免疫反应性（Fos-LI）以及对14C-2-脱氧葡萄糖（2-DG）摄取进行高分辨率放射自显影成像，评估了大脑活动模式对游泳应激的反应。所研究的应激范式是一种用于抗抑郁药物活性的经典行为筛选，即强迫游泳试验。游泳应激产生的最显著影响之一是外侧隔核的一个受限区域内2-DG摄取增加和Fos-LI的诱导。特定的“边缘”皮质区域，包括内侧前额叶、腹外侧眶额和扣带回皮质，对游泳应激也表现出2-DG摄取增加和Fos-LI表达增加。在游泳应激大鼠的下丘脑室旁核中，诱导了Fos-LI，但2-DG摄取没有明显变化。由于所使用的特定游泳应激方案是抗抑郁药物的行为筛选，因此研究了丙咪嗪对应激诱导的2-DG摄取变化和Fos-LI诱导的影响。丙咪嗪治疗可阻断应激诱导的外侧隔核2-DG摄取增加，但丙咪嗪治疗对同一区域Fos-LI的诱导没有影响。在受游泳应激影响的皮质区域，丙咪嗪治疗既未改变2-DG摄取，也未改变Fos-LI表达。在基础条件下单独给予丙咪嗪可在杏仁核中央核和终纹床核背外侧亚区强烈诱导Fos-LI。在这些后一区域，丙咪嗪治疗对2-DG摄取没有明显影响。这些结果为与游泳应激相关的大脑活动地形图模式以及丙咪嗪的神经解剖学选择性作用提供了见解。通过评估Fos-LI和2-DG摄取获得的不同且互补的信息说明了应用这两种功能映射方法来检查行为状态和药物治疗的神经解剖学相关性的实用性。
