Assessment the effects of Metyrapone (as a glucocorticoids synthesis inhibitor) on memory retrieval and reconsolidation in rats

Previous studies have indicated that memory retrieval is impaired under high levels of glucocorticoids as seem in severe stress. In this study, we investigated the effect of peripheral injection of Metyrapone (an inhibitor of glucocorticoid synthesis) on memory retrieval and reconsolidation in rats. I this experimental study 80 Wistar rats (200-220 gr) were trained (1 mA, 3s) in a passive avoidance task. Retention test was done 48hr after training. Metyrapone (25, 50 and 100 mg/kg) or vehicle was injection IP 90 min before of retention test. Memory retention of each animal was measured as latency takes to enter the dark chamber of the task. Also immediately after reactivation, rats were injected with Metyrapone (100 mg/kg) Cycloheximide (2.8 mg/kg as a protein synthesis inhibitor and sham group) and reconsolidation assessed 2, 9, 11 days after memory reactivation, that rats were returned to the context for 10 min, and step-through latency was recorded. The results showed that administration of Metyrapone at doses of 25 and 100mg significantly impaired memory retrieval as compared with control group. No significant effect was found with intermediate dose of Metyrapone (50 mg/kg). Also Metyrapone 100 mg/kg impaired memory reconsolidation. These findings provide evidence that inhibition of glucocorticoid synthesis by Metyrapone impair memory retrieval in a U shape manner and impair reconsolidation in high doses.