Prophylactic efficacy of ketamine, but not the low-trapping NMDA receptor antagonist AZD6765, against stress-induced maladaptive behavior and 4E-BP1-related synaptic protein synthesis impairment.
Prog Neuropsychopharmacol Biol Psychiatry
; 115: 110509, 2022 04 20.
Article
em En
| MEDLINE
| ID: mdl-35033626
ABSTRACT
Ketamine enhances the resilience against stress-induced depressive-like behavior, but its prophylactic efficacy in anxiety-related behaviors remains to be elucidated. Moreover, there is a need for developing novel preventive strategies against depressive- and anxiety-like behavior. AZD6765, a low-trapping NMDA receptor antagonist, shares with ketamine common molecular targets and produces rapid-onset antidepressant effects, suggesting that it could be a prophylactic agent. Therefore, this study investigated the prophylactic effect of ketamine against the depressive- and anxiety-like behavior induced by chronic restraint stress (2â¯h/day, for 10â¯days) in mice. We also investigated if AZD6765 exerts a resilience-enhancing response against these maladaptive behaviors. The contribution of 4E-BP1-related synaptic proteins synthesis (PSD-95/GluA1) in the possible pro-resilience efficacy of ketamine and AZD6765 was investigated. A single administration of ketamine (5â¯mg/kg, i.p.), but not AZD6765 (1 or 5â¯mg/kg, i.p.), given 1â¯week before the stress protocol, was effective in preventing stress-induced depressive-like behavior in the tail suspension test and splash test. Ketamine administered at 1 and 5â¯mg/kg (i.p.), but not AZD6765 (1 or 5â¯mg/kg, i.p.), prevented stress-induced anxiety-related self-grooming alterations. Stress-induced reduction on 4E-BP1 phosphorylation and PSD-95 and GluA1 immunocontent in the prefrontal cortex was prevented by ketamine (5â¯mg/kg, i.p.), but not AZD6765 (1 or 5â¯mg/kg, i.p.). The results indicate that ketamine, but not AZD6765, exerts a pro-resilience response against stress-induced maladaptive behavior, reinforcing that it could be a prophylactic agent to manage individuals at-risk to develop MDD and anxiety.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenetilaminas
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Piridinas
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Restrição Física
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Analgésicos
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Ketamina
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Antidepressivos
Limite:
Animals
Idioma:
En
Revista:
Prog Neuropsychopharmacol Biol Psychiatry
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Brasil