FLUOXETINE EFFECTS ON THE ALTERED SIGNAL TRANSDUCTION OF CRF1 IN AN ANIMAL MODEL OF DEPRESSION

FERNÁNDEZ MACEDO G.V.; SIFONIOS L.; CLADOUCHOS M.L.; WIKINSKI S

Rosario

Congreso; XLI Reunión Anual de la Sociedad Argentina de Farmacología Experimental; 2009

Sociedad Argentina de Farmacología Experimental

In previous works we demonstrated that in the hippocampus of animals exposed to the learned helplessness paradigm (LH) the expression of CRF1 and the MAPK signaling triggered by CRF are reduced. In order to study the pharmacological effect of fluoxetine in these parameters, we evaluated the behavioural response, the levels of CRF1 by in situ hybridization using a cRNA digoxigenin-labeled probe and the activation of ERK1/2 (pERK1/2) by immunofluorescence in the hippocampus of LH rats after 21 days of fluoxetine administration (10mg/kg/day; i.p.). We compared four groups:  C FLX (rats not exposed to stress that received fluoxetine), C SF (rats not exposed to stress that received physiological solution), LH FLX (rats that develop the behavioural despair after exposure to stress and received fluoxetine) and LH SF (rats that develop the behavioural despair after exposure to stress and received physiological solution). LH FLX showed the reversion of the behavioural despair in comparison with LH SF (p<0.05). LH FLX showed no difference with the C FLX group in the mRNA CRF1 expression while LH SF showed a decrease versus C SF (p<0.05).  When we measured the levels of activation of ERK1/2 we found that LH FLX and LH SF showed a decrease versus C FLX and C SF (p<0.05 and p<0.01). We conclude that chronic treatment with fluoxetine reverses the behavioural despair as well as the CRF1 decrement, while fails to exert any effect on pERK1/2 changes.