FLUOXETINE IMPAIRS MEMORY FORMATION BY DOWN-REGULATION OF MITOGEN-ACTIVATED PROTEIN KINASES (MAPK/ERK) mRNA EXPRESSION.

VALERIA PAOLA CARLINI; MARIA BELEN PORETTI; MARTA FIOL DE CUNEO

Cordoba

Congreso; XII Jornada de Investigacion Cientifica; 2011

Secretaria de Ciencia y Tecnologia

  Psychiatric disorders, including depression, are complex and heterogeneous clinical entities. The depressive state is characterized by a core conjunct of psychopathological phenomena, among which the short and long-term memory impairment is included. The launch to fluoxetine market, a selective serotonine reuptake inhibitor, was the beginning of a new era of safe and effective treatment for depression. However, the impact on memory processes has not been elucidated. The purpose of the present study was to investigate, in an experimental model, the fluoxetine effects on memory formation and genes expression related to this processes in hippocampus. Adult male Albino?s Swiss mice were divided in two groups: the control one was orally treated, during 28 days with saline (S) and the problem group with flouxetine (F, 10 mg/Kg/day) and then, in order to determine a depressive behavior the tail suspension test was applied. The last day of treatment, memory retention was evaluated using the objects recognition test and then, the mice were sacrificed and their hippocampi were collected by dissection from both hemispheres, in order to study, using real time PCR, the mRNA MAPK/ERK expression,. The animals treated with fluoxetine showed memory impairment in relation to S animals (F= 39.50, p≤ 0.05, n = 15), a lower expression of to mitogen-activated protein kinases (MAPK/ERK) (F = 6.65, p =0.005, n = 8) and antidepressant behaviour, evidence by reduction in the immobility time in the tail suspension test (F = 8.57, p ≤0.05, n = 15). Results here obtained suggest that fluoxetine effects on memory performance could be mediated by MAPK/ERK down-regulation that probably interferes in the molecular memory pathway.