Effects of the protein synthesis inhibitor cycloheximide on anxiety-like extinction behavior in an animal model of post-traumatic stress

The effect of cycloheximide (CXM), a protein synthesis inhibitor, on memory reconsolidation and extinction was explored in rats using a model of post-traumatic stress. Forty-two animals were exposed to predator stress followed by 1, 2, or 4 extinction trials. Saline or CXM (1 mg/kg) was administered following the last extinction trial and anxiety was measured in the elevated-plus maze (EPM) seventy-two hours later. Saline control animals exhibited elevated anxiety levels in comparison to a no stress control group. Cycloheximide appeared to maintain stress-induced anxiety responses, which otherwise declined with repeated extinction trials in the saline control groups. These findings suggest that cycloheximide may have induced amnesia for extinction, leaving the target memory of the predatory stress intact resulting in elevated levels of anxiety. The relationships between de novo protein synthesis and reconsolidation of anxiety-related memories following extinction trials may be more complex than originally thought.

► The effects of protein synthesis inhibition on extinction training were explored.
► An animal model of Post Traumatic Stress Disorder was utilized prior to extinction training.
► Inhibition of protein synthesis has the ability to block extinction training.
► With extinction blocked, the initial elevation in anxiety remains intact.
► Findings demonstrate de novo protein synthesis as necessary in extinction of a traumatic memory.