EFECTOS DE FLUOXETINA Y VENLAFAXINA SOBRE LA INGESTA DE ALIMENTOS Y LA EXPRESIÓN DE GENES DEL SISTEMA DE RECOMPENSA EN UN MODELO ANIMAL DE DEPRESIÓN

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

Mar del Plata

Congreso; LVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2013

Sociedad Argentina de Investigación Clínica

It has been demonstrated that depression and its treatment induced alteration in the food intake and body weight. In order to provide evidence about the molecular mechanisms underlying the effects of chronic treatment with fluoxetine (F) and venlafaxine (V) on food intake and hedonic behavior, we studied gene expression in the hypothalamus related to these processes in a depression animal model (olfactory bulbectomy-BOB). Adult male Albino?s Swiss mice were divided in two groups: Sham group without BOB and bulbectomized group (OB). Both groups were orally treated, during 28 days with saline (S), F (10 mg/Kg/day) or V (10 mg/Kg/day), n=10 animals/group. Food intake and body weight were daily measured. In order to study the expression of genes using real time PCR, the last day of treatment the mice were sacrificed and their hypothalamus were collected by dissection. The genes analyzed include dynophin synthesis, kappa-opioid receptor (KOR), mu-opioid receptor (MOR) and delta-opioid receptor (DOR). Food intake and body weight gain significantly decreased in OB-S animals with respect to Sham-S (cumulative food intake OB-S=115.75 ± 3.06 g vs. Sham-S=131.17 ± 2.52 g; p<0.001). Fluoxetine and venlafaxine treatment significantly reverts this effect (p<0.001). The gene expression of dynorphin was significantly higher in OB-S than Sham-S (relative expression (AU) OB-S= 2.23 ± 0.03 vs Sham-S= 1.21 ± 0.01; p<0.001). Fluoxetine treatment elicited a significant decrease in dynorphin expression in OB animals with respect to OB-S (AU OB-F= 1.35 ± 0.02 vs. OB-S= 2.23 ± 0.03; p<0.001). The gene expression for KOR and MOR was decreased in OB-F when compared with OB-V (p<0.01). Taking into account that dynorphin system generally promotes anxiety-like behavior and affects feeding, it is possible to suggest that the increment in the expression of this gene in hypothalamus could explain the reduction in food intake and body weight gain in OB-S animals.