Pugh C R, Kumagawa K, Fleshner M, Watkins L R, Maier S F, Rudy J W
University of Colorado, Boulder, Colorado, 80309, USA.
Brain Behav Immun. 1998 Sep;12(3):212-29. doi: 10.1006/brbi.1998.0524.
The reported experiments explore the effects of peripheral LPS administration on learning and memory processes. As measured by the conditioned freezing response, intraperitoneal LPS administration given after conditioning impaired contextual but not auditory-cue fear conditioning in both juvenile (hooded Long Evans) and adult rats (albino Sprague Dawley) of two different strains. This impairment in contextual fear conditioning was not dependent on the presence of the tone. Preexposure to the context eliminated the effect of LPS on contextual fear conditioning, and in addition, LPS given after context preexposure negated the beneficial effects of preexposure on contextual fear. These results suggest that LPS disrupts posttrial memory consolidation processes. In support of the hypothesis that LPS-induced proinflammatory cytokine release is involved in producing the impairment in contextual fear caused by LPS, peripheral interleukin-1 receptor antagonist (IL-1ra) administered subcutaneously at a dose of 100 mg/kg prevented the impairment in contextual fear caused by LPS. These experiments provide evidence for a role of immune activation and cytokine activity in learning and memory processes.
所报道的实验探究了外周给予脂多糖（LPS）对学习和记忆过程的影响。通过条件性僵住反应测量发现，在两种不同品系的幼年（带帽长 Evans 大鼠）和成年大鼠（白化斯普拉格-道利大鼠）中，条件化后腹腔注射 LPS 会损害情境恐惧条件反射，但不影响听觉线索恐惧条件反射。情境恐惧条件反射的这种损害不依赖于音调的存在。预先暴露于情境中可消除 LPS 对情境恐惧条件反射的影响，此外，在情境预先暴露后给予 LPS 会抵消预先暴露对情境恐惧的有益作用。这些结果表明，LPS 会破坏试验后记忆巩固过程。为支持 LPS 诱导的促炎细胞因子释放参与产生 LPS 所致情境恐惧损害这一假说，以 100 mg/kg 的剂量皮下注射外周白细胞介素-1 受体拮抗剂（IL-1ra）可预防 LPS 所致的情境恐惧损害。这些实验为免疫激活和细胞因子活性在学习和记忆过程中的作用提供了证据。
