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

Abstract

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 [Ca] 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.

Non-genomic Actions of Methylprednisolone Differentially Influence GABA and Glutamate Release From Isolated Nerve Terminals of the Rat Hippocampus

“…The hippocampus expresses high amounts of corticosteroid receptors ( de Vargas et al, 2017 ), but so far no attempt has been made to discriminate the effect of GR (low affinity) and MR (high affinity) receptors on transmitters release in this brain region. Pre-treatment of hippocampal nerve terminals either with mifepristone (500 nM) or with spironolactone (500 nM) to block GR and MR, respectively, prevented the facilitatory effect of MP (300 μM) on evoked [14C]Glu release independently of the depolarizing agent being used, either high KCl ( Figure 2Bii ) or VT ( Figure 3Bii ).…”

“…This new vision regarding the molecular mechanisms underlying the differential role of corticosteroids, namely MP, on amino-acid transmitters release, together with the fact that hippocampal neurons abundantly express both MRs and GRs ( Karst et al, 2005 ; Joëls et al, 2012 ), may impact on the rationale for designing new strategies for better treatment of pathological conditions affecting the hippocampus, specifically drug-refractory epilepsy, post-traumatic stress, memory deficits and neurodegenerative diseases. In a recent study from our group, it was proposed that low doses of MP given for a short period of time favored in vivo aversive memory persistence and this was correlated with significant gains in in vitro hippocampal LTP ( de Vargas et al, 2017 ). Hippocampal LTP is highly dependent on neuronal plasticity phenomena that are commonly associated with glutamatergic neurotransmission strengthening.…”

“…Contrariwise, low to moderate doses of corticosterone may enhance LTP ( Diamond et al, 1992 ). Recently, our group proposed MP (5–30 mg/kg, i.p., for 10 days) as a cognitive enhancer in vivo because it favored aversive memory persistence in adult rats, without any effect on exploring behavior, locomotor activity, anxiety levels and pain perception ( de Vargas et al, 2017 ).…”

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

“…The treated animals received a single dose of MP (5 mg/kg) dissolved in saline and administered intraperitoneally according to the group treatment (2 h before or after training and 4 h after training; i.p.). The dose was defined based on previous studies (de Vargas et al, 2017). The control groups received saline (vehicle; i.p).…”

“…On the other hand, a single corticosterone injection after training in a fear conditioning task seems to improve memory consolidation (Abrari et al, 2009). Additionally, our group demonstrated, in previously experiments carried out with rats, that the chronic treatment (10 days) with a low dose of MP (5 mg/kg), but not with a high dose (30 mg/kg), promotes aversive memory persistence, which was correlated to the improvement in long-term potentiation (LTP) (de Vargas et al, 2017). The contradictions found in the MP effects by the various authors can be attributed to the diversity of effects caused by glucocorticoids depending on the different temporal administration or the different doses used in each study.…”