Efectos antidepresivos y plásticos de fluoxetina: papel de BDNF y sus posibles vias de señalización intracelular

RUBIO MC.,WIKINSKI S., REUNÉS A.,BONAVITA C.,CERESETO M.,FERRERO A.

Anales de la Fundación Alberto J. Roemmers Volumen XVII

Fundación Alberto J. Roemmers

Lugar: Buenos Aires; Año: 2006; p. 357 - 368

Abstract OBJECTIVES: The main goals of our work were: to evaluate the effect an inescapable stress- a well knpwn model of depression, on the neurcñ~ cytoskeletal proteins NFL, NFM;11FH (Iight, medium and heavy subunits of re intermediate neurofilaments respectively) and on microtubule associated protein 2 (MAP2); 2)to investigate whether !he chronic treatment with f1uoxetir:~ reverses the changes observed in the above mentioned proteins; 3) to compare !he effects of inescapable stress in cytoskeleton proteins with those induced by the chronic treatment with high doses of glucocorticoids, which is another accepted modal of depression; 4) to explore the consequences of an inescapable stress and of the chronic treatment with fluoxetine in naive and stressed rats on the hippocampal glutamatergic neurotransmission. RESULTS: 1) lnescapable stress induces a signiftcant·diminution in NFL in CA3 and dentate gyrus of hippocampus; 2) chronic exposure ID high dosas of corticosterone induces NFL diminution and afso a significant decrease oÍ NFM, NFH and MAP2. These results are oot due to a decrement in the total number of neurons, as the assessment of this parameter by the immunofluorescence of NeuN, a specific neuronalantibody, showed no effect 01 chronic corticosterone administration; 3) fluoxetine falled to reverse the cytoskeletal changes induced by exposure to inescapable stress; 4) chronic treatment with fluoxetine significantly increased glutarnate release in the hippocampus, which in tum correlates with a diminution in the convulsive threshold. However, this plastic response is not observed in animals exposed to an experimental model of depression.