Corticosterone Impairs Reconsolidation Of Novel Object Recognition Memory In Rats

Objective: Long-term memory formation involves a set of phases such as acquisition, consolidation, reconsolidation and retrieval. Corticosterone, a stress-related hormone, has been suggested to play an important role in modulation of learning and memory through binding to glucocorticoid receptors. For example, administration of corticosterone after memory reactivation impairs the reconsolidation of a contextual conditioned fear memory and drug memory. However, it remains unclear whether corticosterone affects the novel object recognition(NOR) memory reconsolidation. In the present study, we examined the effects of corticosterone on the NOR memory reconsolidation in rats.Methods: Experiment 1 was designed to assess the effect of corticosterone administration immediately after reactivation on NOR memory reconsolidation. The behavioral procedure involved four phases: habituation(day 1 and 2), training(day 3), reactivation(day 4) and test(day 5) for NOR memory. Immediately after reactivation, rats were injected intraperitoneally vehicle or corticosterone(0.1, 1 and 3 mg/kg). On the training and reactivation sessions, the total time spent exploring both objects was recorded. On the test session, the discrimination indexes(DI) were calculated as the difference in exploration time or frequency between novel object and familiar object. Experiment 2 was designed to assess the effect of corticosterone(3 mg/kg) administration 6 h after reactivation on NOR memory reconsolidation. Training procedures were as described in experiment 1, except that rats were injected intraperitoneally vehicle or corticosterone 6 h after reactivation on Day 4. On the training and reactivation sessions, the total time spent exploring both objects was recorded. On the test session, the discrimination indexes(DI) were calculated as the difference in exploration time or frequency between novel object and familiar object. Experiment 3 was designed to assess the effect of corticosterone(3 mg/kg) on NOR memory without reactivation of memory. Training procedures were as described in experiment 1, except that rats were only received intraperitoneally vehicle or corticosterone administration(no reactivation) on Day 4. On the training session, the total time spent exploring both objects was recorded. On the test session, the discrimination indexes(DI) were calculated as the difference in exploration time or frequency between novel object and familiar object. Experiment 4 was designed to assess whether corticosterone(3 mg/kg) affects the nonspecific response(locomotor activity and anxiety level) of rats 24 h after corticosterone administration. The rats received intraperitoneally saline or corticosterone injection. Twenty-four hours after injection, rats were taken from their home cages and transported to the open field test chambers for 5 min and their behaviours were recorded as digital videos. The distance of rat traveling(as locomotor activity index) and the ratio of time spent in the central zone to time spent in the peripheral zone(as anxiety level index) in the open field test chamber were analyzed.Results: In experiment 1, the four groups showed equivalent levels of exploring both objects on the training and reactivation sessions. On the test session, rats with corticosterone at 3 mg/kg presented a significant lower time DI compared with vehicle rats. There was no significant difference in time DI between vehicle rats and rats with corticosterone at o.1 or 1 mg/kg. At the same time, the four groups showed equivalent levels of frequency DI on the test session. In experiment 2, the two groups showed equivalent levels of exploring both objects on the training and reactivation sessions. On the test session, the two groups showed equivalent levels of time and frequency DI. In experiment 3, the two groups showed equivalent levels of exploring both objects on the training session. On the test session, the two groups showed equivalent levels of time and frequency DI. In experiment 4, the two groups showed equivalent levels of the distance of rat traveling and the ratio of time spent in the central zone to time spent in the peripheral zone.Conclusion: Post-reactivation corticosterone administration impairs the reconsolidation of NOR memory. This effect of corticosterone on NOR memory reconsolidation is reactivation-dependent, and presents a specific time-window effect.