Cognitive Deficits Following a Post-Myocardial Infarct in the Rat Are Blocked by the Serotonin-Norepinephrine Reuptake Inhibitor Desvenlafaxine.
Int J Mol Sci
; 19(12)2018 Nov 26.
Article
em En
| MEDLINE
| ID: mdl-30486235
ABSTRACT
Myocardial infarction (MI) in animal models induces cognitive deficits as well as the activation of caspase in the limbic system; both can be blocked by 2 weeks of treatment following MI using tricyclic antidepressants or selective serotonin uptake blockers. Here we used three different treatment schedules to test the short- and long-term effects of the combined serotonin-norepinephrine reuptake inhibitor desvenlafaxine on post-MI-associated cognitive deficits and caspase activation. MI was induced in 39 young adult rats, and 39 rats served as sham-operated controls. Desvenlafaxine (3 mg/kg/day, i.p.) or saline was administered according to one of three schedules (1) for 2 weeks, starting right after surgery; (2) for 16 weeks, starting 2 weeks after surgery; (3) for 16 weeks, starting right after surgery. Behavior was tested 2 weeks (social interaction, passive avoidance) and 16 weeks (forced swimming, Morris water maze) after surgery. Caspase-3 and caspase-6 activities were measured 16 weeks after surgery. At 2 and 16 weeks post-surgery, saline-treated MI rats displayed performance deficits compared to desvenlafaxine-treated rats, regardless of the treatment schedule. Caspase-3 activity was higher in the amygdala (medial and lateral) and hippocampal CA3 region in untreated MI rats, whereas caspase-6 activity was higher in the CA1 region. Caspase-6 activity correlated positively with deficits in the Morris water maze. These results indicate that, independently of treatment schedules, various treatment schedules with desvenlafaxine can prevent MI-associated cognitive deficits and decrease caspase activities in the limbic system.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Norepinefrina
/
Inibidores Seletivos de Recaptação de Serotonina
/
Transtornos Cognitivos
/
Succinato de Desvenlafaxina
/
Infarto do Miocárdio
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article