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Ketamine, but not guanosine, as a prophylactic agent against corticosterone-induced depressive-like behavior: Possible role of long-lasting pro-synaptogenic signaling pathway.

Abstract：

:Ketamine has been reported to exert a prophylactic effect against stress-induced depressive-like behavior by modulating the guanosine-based purinergic system. However, the molecular pathways underlying its prophylactic effect and whether guanosine also elicits a similar effect remain to be determined. Here, we investigated the prophylactic effect of ketamine and guanosine against corticosterone (CORT - 20 mg/kg, p.o.)-induced depressive-like behavior in mice. Furthermore, we characterized if the prophylactic response may be associated with mTORC1-driven signaling in the hippocampus and prefrontal cortex. A single administration of ketamine (5 mg/kg, i.p.), but not guanosine (1 or 5 mg/kg, p.o.), given 1 week before the pharmacological stress prevented CORT-induced depressive-like behavior in the tail suspension test (TST) and splash test (SPT). Fluoxetine treatment for 3 weeks did not prevent CORT-induced behavioral effects. A single administration of subthreshold doses of ketamine (1 mg/kg, i.p.) plus guanosine (5 mg/kg, p.o.) partially prevented the CORT-induced depressive-like behavior in the SPT. Additionally, CORT reduced Akt (Ser473) and GSK-3β (Ser9) phosphorylation and PSD-95, GluA1, and synapsin immunocontent in the hippocampus, but not in the prefrontal cortex. No alterations on mTORC1/p70S6K immunocontent were found in both regions in any experimental group. CORT-induced reductions on PSD-95, GluA1, and synapsin immunocontent were prevented only by ketamine treatment. Collectively, these findings suggest that ketamine, but not guanosine, exerts a prophylactic effect against depressive-like behavior, an effect associated with the stimulation of long-lasting pro-synaptogenic signaling in the hippocampus.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Camargo A,Dalmagro AP,de Souza MM,Zeni ALB,Rodrigues ALS

doi

10.1016/j.expneurol.2020.113459

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

113459

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(20)30290-9

journal_volume

334

pub_type

杂志文章

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Ketamine, but not guanosine, as a prophylactic agent against corticosterone-induced depressive-like behavior: Possible role of long-lasting pro-synaptogenic signaling pathway.