A Single Dose of Methylprednisolone Improves Aversive Memory Consolidation and Extinction in Rats.

Aversive memory is essential for survival, but in some situations its exacerbation can be potentially dangerous. There are several ways to modulate memory, among them, through stress-related hormones physiological release or administration of exogenous substances analogous to them. Recently, our group shown that a chronic treatment with a low dose of methylprednisolone (MP) is able to promote memory persistence in rats. Herein, we evaluate if a single intraperitoneal (IP) dose of MP (5 mg/kg) is able to modulate aversive memory consolidation and promote memory persistence and extinction in rats. For this, two experiments were carried out. In the first one, we demonstrated that a single IP MP administration in specific times after inhibitory avoidance (IA) training improved memory consolidation and persistence. In the second experiment, we verified that a single IP MP administration 2 h after IA extinction training promoted memory extinction. This results suggest a possible new clinical applicability for MP on the aversive memory disorders, as post-traumatic stress.

Methylprednisolone as a memory enhancer in rats: Effects on aversive memory, long-term potentiation and calcium influx.

It is well recognized that stress or glucocorticoids hormones treatment can modulate memory performance in both directions, either impairing or enhancing it. Despite the high number of studies aiming at explaining the effects of glucocorticoids on memory, this has not yet been completely elucidated. Here, we demonstrate that a low daily dose of methylprednisolone (MP, 5mg/kg, i.p.) administered for 10-days favors aversive memory persistence in adult rats, without any effect on the exploring behavior, locomotor activity, anxiety levels and pain perception. Enhanced performance on the inhibitory avoidance task was correlated with long-term potentiation (LTP), a phenomenon that was strengthen in hippocampal slices of rats injected with MP (5mg/kg) during 10days. Additionally, in vitro incubation with MP (30-300µM) concentration-dependently increased intracellular [Ca2+]i in cultured hippocampal neurons depolarized by KCl (35mM). In conclusion, a low daily dose of MP for 10days may promote aversive memory persistence in rats.