Glibenclamide treatment prevents depressive-like behavior and memory impairment induced by chronic unpredictable stress in female mice.
Behav Pharmacol
; 32(2&3): 170-181, 2021 04 01.
Article
en En
| MEDLINE
| ID: mdl-33079735
ABSTRACT
Glibenclamide is a second-generation sulfonylurea used in the treatment of Type 2 Diabetes Mellitus. The primary target of glibenclamide is ATP-sensitive potassium channels inhibition; however, other possible targets include the control of inflammation and blood-brain barrier permeability, which makes this compound potentially interesting for the management of brain-related disorders. Here, we showed that systemic treatment with glibenclamide (5 mg/kg, p.o., for 21 days) could prevent the behavioral despair and the cognitive dysfunction induced by chronic unpredictable stress (CUS) in mice. In nonhypoglycemic doses, glibenclamide attenuated the stress-induced weight loss, decreased adrenal weight, and prevented the increase in glucocorticoid receptors in the prefrontal cortex, suggesting an impact in hypothalamic-pituitary-adrenal (HPA) axis function. Additionally, we did not observe changes in Iba-1, NLRP3 and caspase-1 levels in the prefrontal cortex or hippocampus after CUS or glibenclamide treatment. Thus, this study suggests that chronic treatment with glibenclamide prevents the emotional and cognitive effects of chronic stress in female mice. On the other hand, the control of neuroinflammation and NLRP3 inflammasome pathway is not the major mechanism mediating these effects. The behavioral effects might be mediated, in part, by the normalization of glucocorticoid receptors and HPA axis.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Estrés Psicológico
/
Gliburida
/
Depresión
/
Hipoglucemiantes
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Behav Pharmacol
Asunto de la revista:
CIENCIAS DO COMPORTAMENTO
/
FARMACOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Brasil