Banca de DEFESA: THIEZA GRAZIELLA ARAUJO DA SILVA GOES DE MELO

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : THIEZA GRAZIELLA ARAUJO DA SILVA GOES DE MELO
DATA : 27/07/2016
HORA: 09:00
LOCAL: Sala de Aula da Pós-Graduação em Psicobiologia
TÍTULO:

Estrous cycle and sex on acute fluoxetine interactions on the modulation of memory and anxiety- and depression-like behaviors in rats

PALAVRAS-CHAVES:

Discriminative avoidance task; forced swimming test; antidepressants; fluoxetine; estrous cycle.

PÁGINAS: 145
GRANDE ÁREA: Ciências Humanas
ÁREA: Psicologia
RESUMO:

Mood and anxiety disorders have great incidence among world population and present high comorbidity. Important cognitive alterations are present in both pathologies, besides the respective emotional characteristics. The main pharmacological treatment for both mood and, to some extent, anxiety disorders are the antidepressants, mainly selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI). Even though women are almost twice more affected by these disorders than men, pre-clinical research on the effects of antidepressants on this sex is not as representative as in male subjects. Further, possible influences of the natural female hormonal cycle on the action of these drugs have been poorly explored. Our study aimed to investigate the acute effects of fluoxetine on the behavior of female rats at different phases of the estrous cycle, using the plus-maze discriminative avoidance (PMDAT) and forced swimming (FS) tests. The PMDAT is held in a modified elevated plus-maze that allows concomitant evaluation of memory and anxiety. We used the exploration of the aversive enclosed arm (relative to the non-aversive enclosed arm) to evaluate acquisition, retrieval and extinction of the task in training, test and retest sessions, respectively. The exploration of the open arms was used as a measure of anxiety-like behavior. The FS was performed in two sessions (training and test) in which we evaluated the decrease in immobility duration and the increase in climbing in rats submitted to a water-filled cylinder as indicatives of an antidepressant effect. Fluoxetine (5, 10 and 20 mg/ml/kg) or vehicle were given acutely i.p. to female rats at different cycle phases, previously to the training session (PMDAT, experiments 1 and 2), after the training session (PMDAT, experiment 3) or prior to the test session (experiments 4 – PMDAT and 5 – FS). Animals were tested (PMDAT and FS) and retested (PMDAT) 24 h and 48 h after the training session, respectively. The main results obtained in PMDAT showed that: (1) neither fluoxetine administration nor cycle phase interfered with acquisition; (2) pre-training fluoxetine impaired retrieval (test session) in male, but not female rats (if all cycle phases were taken together for analysis); (3) the effects of pre-training fluoxetine in female varied according to fluoxetine dose and cycle phase: for example, no effects were detected in proestrus, and an improvement and decrease in retrieval were observed when rats were trained in estrus, depending on the dose; (4) corroborating an effect on the consolidation of the task, post-training fluoxetine induced a more ample (irrespective of cycle phase) retrieval deficit (test session); pre-test treated female rats presented retrieval deficits irrespective of phase or treatment (including vehicle), indicating an effect of the injection procedure, but we could still observe a decrease in retrieval caused by fluoxetine; (6) corroborating previous data, extinction of the task (retest session) is more expressive in males, and in females it depends on the cycle phase during training and the protocol of administration; and (7) in general, fluoxetine induced a decrease in open-arms exploration indicating an anxiogenic effect, which was more prominent at some cycle phases. Nevertheless, due to different dose ranges and cycle phases in which these alterations appeared, the drug effects on memory and anxiety do not seem to be related to each other. Regarding the results from FS, no effects of fluoxetine were detected when all phases were considered together for analysis, which is expected after an acute treatment. However, we found an increase in depressive-like behavior in animals in proestrus treated with fluoxetine. While this effect might be related with the anxiogenic effect found in the PMDAT, it is worth mentioning that females in proestrus, irrespective of treatment, present a basal alteration in this test. In conclusion, the results suggest that the acute effects of fluoxetine on memory vary according to the estrous cycle phase, as well as the memory phase in which it was administered. In addition, anxious- and depressive-like behaviors were observed in female rats, under certain conditions, after fluoxetine treatment. Despite clinical and animal studies show antidepressant and anxiolytic beneficial effects of fluoxetine prolonged treatment, the present results suggest possible cognitive and emotional acute side effects which may be influenced by sex and hormonal state.

MEMBROS DA BANCA:
Interno - 264.038.248-99 - ALESSANDRA MUSSI RIBEIRO - UNIFESP
Interno - 1645202 - ELAINE CRISTINA GAVIOLI
Externo à Instituição - FLAVIO FREITAS BARBOSA - UFPB
Presidente - 187.472.708-29 - REGINA HELENA DA SILVA - UNIFESP
Externo ao Programa - 1720860 - VANESSA DE PAULA SOARES RACHETTI