Corticosterone injection into the dorsal and ventral hippocampus impairs fear memory reconsolidation in a time-dependent manner in rats

Abstract

Reconsolidation is an active process induced following the reactivation of previously consolidated memories. Recent studies suggest brain corticosteroid receptors may participate in the modulation of fear memory reconsolidation. Glucocorticoid receptors (GRs), with 10-fold lower affinity than mineralocorticoid receptors (MRs), are mainly occupied during the peak of the circadian rhythm, and after stress, so they probably have a more critical role than MRs in memory phases during stressful situations. This study investigated the role of dorsal and ventral hippocampal (DH and VH) GRs and MRs on fear memory reconsolidation in rats. Male Wistar rats with surgically implanted bilaterally cannulae at the DH and VH were trained and tested in an inhibitory avoidance task. The animals received bilateral microinjections of vehicle (0.3 µl/side), corticosterone (3 ng/0.3 µl/side), the GRs antagonist RU38486 (3 ng/0.3 µl/side), or the MRs antagonist spironolactone (3 ng/0.3 µl/side) immediately after memory reactivation. Moreover, drugs were injected into VH 90 min after memory reactivation. Memory tests were performed 2, 9, 11, and 13 days after memory reactivation. Results indicated that injection of corticosterone into the DH but not VH immediately after memory reactivation significantly impaired fear memory reconsolidation. Moreover, corticosterone injection into VH 90 min after memory reactivation impaired fear memory reconsolidation. RU38486, but not spironolactone reversed these effects. These findings indicate that corticosterone injection into the DH and VH via GRs activation impairs the reconsolidation of fear memory in a time-dependent manner.