The chemotherapy agent oxaliplatin impairs the renewal of fear to an extinguished conditioned stimulus in rats

Abstract

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.