doctoralThesis
Depressão experimental induzida pela administração única e repetida dexametasona em camundongos: ferramenta para estudo do potencial antidepressivo de antagonistas NOP
Fecha
2018-12-14Registro en:
SOUZA, Ingrid Brasilino Montenegro Bento de. Depressão experimental induzida pela administração única e repetida dexametasona em camundongos: ferramenta para estudo do potencial antidepressivo de antagonistas NOP. 2018. 125f. Tese (Doutorado em Psicobiologia) - Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, 2018.
Autor
Souza, Ingrid Brasilino Montenegro Bento de
Resumen
Major depression can be triggered by stressful events which deregulate the hypothalamicpituitary-adrenal axis (HPA) response, thus promoting in some circumstances sustained
elevation of circulating glucocorticoid levels. Hypersecretion of glucocorticoids may alter
the functionality of glucocorticoid (rG) receptors at the central nervous system, mainly at
the HPA axis and hippocampus, causing behavioral abnormalities in depressive patients.
Clinical and preclinical findings suggest antidepressant effects due to the blockade of the
NOP receptor signaling. This study aimed to investigate the behavioral actions of acute
and chronic administration of dexamethasone in mice and the effects of the NOP receptor
antagonist, SB-612111, in this experimental model. Male and female Swiss mice were
used to develop this study. The depressive-like behavior of mice was evaluated in the tail
suspension test (TST), splash test and social interaction test. In addition, mouse
spontaneous locomotor activity was assessed in the open field test. Dexamethasone (64
μg/kg, sc) induced depressive-like behavior in mice of both sexes, by increasing the
immobility time in the TST, self-cleaning latency in the splash test, and reducing the
frequency of interactions with an unknown animal in the social interaction test. Treatment
with the antidepressants nortriptyline and venlafaxine (both 30 mg/kg, ip) reversed most
of these behaviors, except for reduced social interaction. Dexamethasone acutely
administered did not affect mouse spontaneous locomotion. However, nortriptyline and
venlafaxine significantly reduced the total distance moved mainly in male mice. The
treatment with the NOP antagonist reversed the depressive-like behavior of acute
dexamethasone in the TST and reduced the latency for self-cleaning in the splash test,
without affecting spontaneous locomotion in male mice. Additionally, dexamethasone
(16 μg/kg, sc) was administered for 14 days and mouse behaviors were measured once a
week. In the first seven days, the repeated administration of dexamethasone increased
immobility time in the TST, and the latency to self-cleaning in the splash test, without
altering the spontaneous locomotion. After 14 days of dexamethasone administration, the
repeated administration of imipramine (during the last 7 days, 20 mg/kg, ip) reversed the
increase in the immobility time in the TST and the elevation in the latency to self-cleaning
in the splash test. In conclusion, acute and repeated administration of dexamethasone
induces depressive-like effects which were reversed by classical antidepressants and NOP
antagonist (acutely). These findings contribute to adding new evidence for a
neuroendocrine model of depression able to be performed in mice of both sexes.
Ultimately, our data reinforce the growing body of information about the therapeutic
potential of NOP antagonists in the treatment of depression.