Banca de DEFESA: INGRID BRASILINO MONTENEGRO BENTO DE SOUZA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : INGRID BRASILINO MONTENEGRO BENTO DE SOUZA
DATA : 14/12/2018
HORA: 08:30
LOCAL: Anfiteatro das Aves
TÍTULO:

Experimental depression induced by acute and repeated administration of dexamethasone in mice: an appliance for studying the antidepressant potential of NOP antagonists

PALAVRAS-CHAVES:

Dexamethasone, Glucocorticoid receptors, Major Depression, Animal model, Nociceptin /Orphanin FQ.

PÁGINAS: 126
GRANDE ÁREA: Ciências Humanas
ÁREA: Psicologia
RESUMO:

Major depression can be triggered by stressful events which deregulate the hypothalamic-pituitary-adrenal axis response, promoting, in some circumstances, sustained elevation of circulating glucocorticoid levels. Hypersecretion of glucocorticoids may alter the functionality of glucocorticoid (rG) receptors at the CNS level, especially on the HPA axis and the hippocampus, generating behavioral abnormalities observed in patients with depression. Clinical and preclinical findings suggest antidepressant effects due to the blockade of the NOP receptor signaling. This study aimed to investigate the behavioral effects of acute and chronic administration of dexamethasone in mice and the NOP receptor antagonist, SB-612111, in this experimental model. Male and female Swiss mice were used. The behavior of the depressive type was evaluated through the Tail Suspension Test (TSC), the splash test and the social interaction test; in addition, the spontaneous locomotor activity of the mice was measured in the open field. Dexamethasone (64 μg / kg, sc) was capable of altering the behavior of the mice, inducing a depressive-like state in males and females, by increasing TSC immobility time, self-cleaning latency in the splash test, and reduce the frequency of interactions with an unknown animal. Treatment with the anti-depressants Nortiptilin (i.p) and Venlafaxine (i.p) reversed most of these behaviors, except for social interaction. Also, acutely administered dexamethasone did not affect the spontaneous lomocoção of the animals, however the acute administration of Nortiptilina and Venlafaxina significantly reduced the distance covered. In addition, the data point to similar behavioral change in males and females, thus characterizing this protocol as a good inducer of experimental depression. NOP receptor antagonist treatment reversed the depressive-like behavior caused by the acute administration of dexamethasone in the TSC and reduced the latency for self-cleaning in the splash test, without altering the locomotion of the mice. For the repeated protocol, dexamethasone (16 μg / kg, s.c.) was administered for 14 days and the behavior measured at two times (eighth and sixteenth day). In the first seven days, dexamethasone showed a depressive type profile responding with elevated immobility in the TSC and increased latency in the splash test without altering the locomotion in the open field. After administration of dexamethasone for an additional 7 days, treatment with Imipramine was able to reverse the increase in immobility in TSC and increase latency in the splash test. In conclusion, this data suggests that acute and repeated dexamethasone induces depressive-like effects which are reversed by conventional antidepressants and NOP antagonist (acutely). In addition to being an effective protocol in males and females for the induction of experimental depression caused by stress. Ultimately, these data provide evidence of the therapeutic potential of NOP antagonists in the treatment of depression.

MEMBROS DA BANCA:
Presidente - 1645202 - ELAINE CRISTINA GAVIOLI
Interno - 2140860 - ROVENA CLARA GALVAO JANUARIO ENGELBERTH
Externo ao Programa - 1720860 - VANESSA DE PAULA SOARES RACHETTI
Externo à Instituição - FLAVIO FREITAS BARBOSA - UFPB
Externo à Instituição - IRIS UCELLA DE MEDEIROS - EBSERH