Department of Psychology, University of Western Ontario, London, Ontario, Canada N6A 5C2.
Brain Behav Immun. 2013 Jan;27(1):123-32. doi: 10.1016/j.bbi.2012.10.005. Epub 2012 Oct 12.
Anticipatory nausea is a classically conditioned response to a context that has been previously paired with toxin-induced nausea and/or vomiting. When injected with a nausea-inducing drug, such as lithium chloride (LiCl), rats will show a distinctive conditioned gaping response that has been suggested to be an index of nausea. Previous studies have found that immune system activation with an endotoxin, such as lipopolysaccharide (LPS), attenuates LiCl-induced conditioned gaping in rats. The present study examined the acquisition of LiCl-induced conditioned gaping in rats that were either LPS tolerant or LPS non-tolerant, as little is known about the effects of endotoxin tolerance on learning and memory. Male Long-Evan rats were given four systemic injections of LPS (200 μg/kg) or isotonic saline (NaCl) to induce LPS tolerance, indexed with 24 h changes in body weight following treatment. The animals were then given 4 acquisition trials in a LiCl-induced conditioned gaping paradigm. On conditioning days animals were treated with LPS (200 μg/kg) or saline followed 90 min later by injection of LiCl (127 mg/kg) or saline and then placed in a distinctive context for 30 min and their behavior video-recorded. On a drug free test day all animals were again placed in the distinctive context for 10 min and behavior was video-recorded. Gaping responses were scored for all acquisition days and the test day. Spleen and body weights were also obtained for all rats at the end of the experiment. Gaping responses were attenuated in rats treated with LPS in both the LPS tolerant and LPS non-tolerant groups. There were significant negative correlations between spleen weight as well as spleen/body weight ratios, and levels of conditioned gaping responses in LiCl treated rats, but not control rats. These results show that LPS interferes with learning/memory in the anticipatory nausea paradigm in rats that are both LPS tolerant and LPS non-tolerant.
预期性恶心是一种经典的条件反射，对先前与毒素引起的恶心和/或呕吐相关的环境做出反应。当给老鼠注射引起恶心的药物，如氯化锂（LiCl）时，它们会表现出一种独特的条件性张口反应，这种反应被认为是恶心的指标。先前的研究发现，用内毒素，如脂多糖（LPS）激活免疫系统会减轻大鼠 LiCl 诱导的条件性张口。本研究检查了 LPS 耐受或不耐受的大鼠对 LiCl 诱导的条件性张口的获得，因为对内毒素耐受对学习和记忆的影响知之甚少。雄性 Long-Evan 大鼠接受了四次 LPS（200 μg/kg）或等渗盐水（NaCl）的全身注射，以诱导 LPS 耐受，用治疗后 24 小时的体重变化来标记。然后，动物在 LiCl 诱导的条件性张口范式中接受了 4 次获得试验。在条件化日，动物接受 LPS（200 μg/kg）或盐水处理，90 分钟后注射 LiCl（127 mg/kg）或盐水，然后将其置于独特的环境中 30 分钟，并对其行为进行视频记录。在无药物测试日，所有动物再次被放置在独特的环境中 10 分钟，并对其行为进行视频记录。在所有获得日和测试日都对张口反应进行评分。实验结束时还获得了所有大鼠的脾脏和体重。在 LPS 耐受和 LPS 不耐受的大鼠中，LPS 处理都减弱了 LiCl 处理大鼠的张口反应。在 LiCl 处理的大鼠中，脾脏重量以及脾脏/体重比值与条件性张口反应水平之间存在显著的负相关，但在对照大鼠中则没有。这些结果表明，LPS 干扰了 LPS 耐受和不耐受的大鼠在预期性恶心范式中的学习/记忆。
