The resilient phenotype elicited by ketamine against inflammatory stressors-induced depressive-like behavior is associated with NLRP3-driven signaling pathway.
J Psychiatr Res
; 144: 118-128, 2021 12.
Article
em En
| MEDLINE
| ID: mdl-34619490
ABSTRACT
Ketamine has emerged as a prophylactic agent against depressive-like behavior induced by stress. However, the possible pro-resilience effects of ketamine against inflammatory stressors-induced depressive-like behavior and the signaling pathways associated with this response remain to be determined. Therefore, this study investigated the ability of prophylactic ketamine administration to produce a pro-resilience effect against the depressive-like behavior induced by lipopolysaccharide (LPS - 0.83 mg/kg, i.p.) and tumor necrosis factor-alpha (TNF-α - 0.1 fg/site, i.c.v.) administration in mice. The possible contribution of the NLRP3 inflammasome-driven signaling pathway to this effect was evaluated in the ventral hippocampus. A single administration of ketamine (5 mg/kg, i.p.) given 1 week before the LPS or TNF-α administration prevented the depressive-like behavior induced by these inflammatory stressors in the tail suspension test (TST) and splash test (SPT). On the other hand, a lower dose of ketamine (1 mg/kg, i.p.) failed to produce a similar effect. The administration of LPS, but not TNF-α, increased the immunocontent of the microglial marker Iba-1 in the ventral hippocampus. LPS increased the immunocontent of all proteins related to NLRP3 signaling, namely ASC, NLRP3, TXNIP, cleaved caspase-1, and IL-1ß in this brain region, while TNF-α only increased ASC and NLRP3 immunocontent. Ketamine administered at the dose of 5 mg/kg, but not at 1 mg/kg, prevented the increase on the immunocontent of NLRP3 inflammasome complex components and regulators induced by LPS or TNF-α administration. Collectively, these findings suggest that ketamine elicits a pro-resilient phenotype against inflammatory stressors-induced depressive-like behavior, an effect associated with the suppression of the NLRP3 inflammasome-driven signaling pathway.
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MEDLINE
Assunto principal:
Proteína 3 que Contém Domínio de Pirina da Família NLR
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Ketamina
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article