Department of Psychology, University of Western Ontario, London, Ontario, Canada N6A5C2.
Physiol Behav. 2012 May 15;106(2):243-51. doi: 10.1016/j.physbeh.2012.02.005. Epub 2012 Feb 9.
The effects of the bacterial endotoxins, lipopolysaccharide (LPS) and muramyl dipeptide (MDP; Experiment 1), and the viral mimetic, polyinosinic: polycytidylic acid (poly I:C; Experiment 2), on the acquisition of "conditioned gaping" behavior in the rodent model of LiCl-induced anticipatory nausea were examined. Experimentally naïve adult male Long-Evans rats were injected (intraperitoneal, i.p.) with either 200 μg/kg LPS, 1.6 mg/kg MDP, or 0.9% saline (Experiment 1), or 4.0 mg/kg poly I:C or 0.9% saline (Experiment 2), 90 min prior to treatment with 127 mg/kg LiCl or saline control and immediately placed into a distinctive context for 30 min (repeated over 4 conditioning days, spaced 72 h apart). On a drug-free test day (72 h following conditioning day 4), each animal was re-exposed to the context for 10 min, and orofacial and aversive behavioral responses were video recorded and analyzed. The results showed that pre-treatment with LPS, MDP (Experiment 1), or poly I:C (Experiment 2) prior to LiCl+context conditioning significantly impaired the establishment of conditioned gaping behavior, thus blocking the acquisition of anticipatory nausea. Results varied in regards to peripheral acute-phase response sickness behaviors, with significantly reduced weight loss in LPS-treated animals, less robust weight loss in poly I:C-treated animals, and no significant reductions in body weight in MDP-treated animals. The learning impairments observed in the current study suggest that endotoxin treatment with bacterial and viral endotoxin may have stronger central effects on learning and memory behavior, relative to peripheral effects on body weight and other sickness-related responses.
本研究旨在探讨细菌内毒素脂多糖（LPS）和胞壁酰二肽（MDP；实验 1）以及病毒模拟物聚肌苷酸-聚胞苷酸（poly I:C；实验 2）对锂盐诱导预期性恶心啮齿动物模型中“条件性张口”行为习得的影响。实验采用成年雄性 Long-Evans 大鼠，首先腹腔注射 200μg/kg LPS、1.6mg/kg MDP 或 0.9%生理盐水（实验 1），或者 4.0mg/kg poly I:C 或 0.9%生理盐水（实验 2），90min 后给予 127mg/kg 锂盐或生理盐水对照处理，并立即置于特定环境中 30min（重复 4 个条件化日，间隔 72h）。在无药物测试日（条件化第 4 天 72h 后），每个动物重新暴露于环境中 10min，通过视频记录和分析口面部和厌恶行为反应。结果显示，锂盐+环境条件化前预先给予 LPS、MDP（实验 1）或 poly I:C（实验 2）可显著损害条件性张口行为的建立，从而阻断预期性恶心的习得。外周急性期反应性疾病行为的结果存在差异，LPS 处理组动物体重明显减轻，poly I:C 处理组动物体重减轻幅度较小，而 MDP 处理组动物体重无明显减轻。本研究中观察到的学习障碍表明，与体重和其他与疾病相关的反应的外周效应相比，细菌和病毒内毒素的内毒素处理可能对学习和记忆行为具有更强的中枢效应。
