ALTERED RESPONSE TO FLUOXETINE TREATMENT IN MICE EXPOSED TO CHRONIC STRESS FED A HIGH-FAT DIET. BEHAVIORAL AND METABOLIC CONSEQUENCES

MARCONE, MP.; GONZALEZ MURANO, MR.; ROMEO, H.; GENARO, AM.; WALD, MR.

Mar del Plata

Congreso; LVIII Reunion Anual de la Asociacion Argentina de Farmacologia Experimental (AAFE); 2023

Sociedad Argentina de Investigacion Clinica (SAIC)

In recent decades,overweight and obesity have become a growing health problem. Among the mainfactors involved in the etiopathology of this disease are the consumption ofhigh-fat diets (HFD) and exposure to chronic stress (CS). In this context, theaim of this work was to investigate the effect of treatment with fluoxetine(FLX) -an antidepressant drug- in normal diet (ND) and HFD fed mice exposed toCS on anxious behavior and its possible metabolic consequences. Taking intoaccount that HFD promotes alterations in lipid metabolism and considering theimportance of the liver in this metabolism, we studied liver histopathology. Inaddition, translocation of intestinal bacteria is known to favor inflammationand hepatic fibrosis, therefore the presence of bacteria through colony formingunit (CFU) counts in the liver was determined. For these studies, C57Bl/6J micewere fed ND or homemade HFD for 6 months and exposed or not to CS/FLX for 4month. Animals exposed to CS with both diets show a higher level of anxiety inopen field, tail suspension and marbel test (p<0.05). FLX treatment reversedthis effect in ND-fed but not in HFD-fed mice (p<0.05). A significantincrease in body weight and plasma cholesterol levels was observed with HFDfeeding (p<0.05). Histological analysis of the liver with hematoxylin andeosin staining indicated a higher steatosis, inflammation and fibrosis score inHFD-fed mice. This score was aggravated by fluoxetine administration in HFD-fedmice and improved in ND-fed mice (p<0.05). Similar results were obtained forthe frequency and number of CFU in the liver. In conclusion, HFD and CS inducemetabolic and behavioral alterations that improved in ND-fed but not in HFD-fedmice. These results point to the need for further studies to evaluate theusefulness of treating anxiety with fluoxetine in patients with obesity andexposed to stressful events.