Glucocorticoids Interact with Cholinergic System in Impairing Memory Reconsolidation of an Inhibitory Avoidance Task in Mice

Introduction: Recent studies suggest that glucocorticoids modulate memory reconsolidation. Moreover, cholinergic system is involved in memory reconsolidation. Since glucocorticoids interact with brain cholinergic system in modulating memory processing, we investigated whether glucocorticoid influences on the reconsolidation of emotionally arousing training depend on the cholinergic system. Methods: Mice were trained (1mA, 3s footshock) in an inhibitory avoidance task. Forty-eight hours after training, memory reactivation was occurred (Test 1), and different treatments were given. Two (Test 2), five (Test 3), and seven days (Test 4) after memory reactivation (Test 1), animals were retested for fear memory retention. Results: In the first experiment, we observed that administration of corticosterone (CORT, 0.3, 1 and 3 mg/kg) following memory reactivation impaired subsequent expression of memory in a dose-dependent manner. In the second experiment, we found that CORT-induced impairment of memory reconsolidation was reversed by the muscarinic receptor antagonist atropine (0.5 and 2 mg/kg). In the third experiment, the nicotinic receptor antagonist mecaylamine (0.5 or 2 mg/kg) was not able to block the corticosterone response. Discussion: These findings indicate that glucocorticoids impair memory reconsolidation by a muscarinic cholinergic mechanism.