School of Psychology, University of NSW, Australia.
Behav Brain Res. 2012 Feb 1;227(1):295-9. doi: 10.1016/j.bbr.2011.11.005. Epub 2011 Nov 15.
Recent evidence has shown that diverse chemotherapy agents can induce cognitive impairments and neurotoxic damage to the central nervous system. Oxaliplatin (OXP), a platinum compound, has been linked with acute and chronic peripheral neuropathies. This study explored the cognitive impacts of OXP in the rat with a fear conditioning procedure. 10 days prior to conditioning and testing, rats received an intraperitoneal injection of OXP (12 mg/kg). On the first day of conditioning, the rats were conditioned to two CSs (CS-ren and CS-ext) in one set of chambers (context A). They then received three tests on separate days. First, the rats were assessed for contextual fear conditioning in context A. Next, the CSs were presented 20 times in a new context (B) until fear conditioning had extinguished. Finally, one of the CSs (CS-ext) was tested again in the extinction context (B), and the other (CS-ren) presented in a new context (C). Results showed that OXP had no effect on the ability of rats to express fear to the conditioning context (A), or on the expression and extinction of conditioned fear to either CS when presented in a second context (B). However, the administration of OXP did impair the ability of rats to renew levels of conditioned fear to CS-ren when this CS was presented in a novel context (C) following extinction. This profile of impairment is consistent with hippocampal damage, and may also involve frontal cortical, amygdalar and thalamic regions important for context discrimination and the contextual modulation of behaviour.
最近的证据表明，多种化疗药物会导致中枢神经系统的认知障碍和神经毒性损伤。奥沙利铂（OXP）是一种铂类化合物，与急性和慢性周围神经病变有关。本研究通过恐惧条件反射程序探讨了 OXP 对大鼠认知的影响。在条件反射和测试前 10 天，大鼠接受奥沙利铂（12mg/kg）腹腔注射。在条件反射的第一天，大鼠在一组室（A 环境）中接受两种 CS（CS-ren 和 CS-ext）的条件反射。然后，它们在单独的三天内接受了三次测试。首先，在 A 环境中评估大鼠的情境恐惧条件反射。接下来，在新环境（B）中呈现 CS 20 次，直到恐惧条件反射消失。最后，在消退环境（B）中再次测试一个 CS（CS-ext），并在新环境（C）中呈现另一个 CS（CS-ren）。结果表明，OXP 对大鼠表达对条件反射环境（A）的恐惧能力没有影响，也对呈现于第二个环境（B）时两个 CS 的条件恐惧表达和消退没有影响。然而，OXP 的给药确实损害了大鼠在消退后，当该 CS 在新环境（C）中呈现时，重新表达 CS-ren 条件恐惧的能力。这种损伤模式与海马损伤一致，也可能涉及额皮质、杏仁核和丘脑区域，这些区域对辨别环境和行为的环境调节很重要。
