Behavioral Profile Assessment in Offspring of Swiss Mice Underwent to Neonatal Treatment with D‐fenfluramine

Abstract

Serotonin (5‐HT) exerts an important role in the central nervous system embryogenesis of mammals, influencing directly several brain systems ontogeny. Therefore, we investigate the effect of neonatal D‐fenfluramine (D‐fen), a specific 5‐HT‐releasing agent, administration on the behavioral expression of adults male Swiss mice. For this purpose, three groups (n=6 each, and ~35g) of pregnant female Swiss mice were mated. The offsprings obtained were treated subcutaneously (s.c) with saline and D‐fenfluramine (1mg/kg or 3mg/kg) from the 5th at 21th post‐natal day. By completing 70 days of life, the animals underwent a behavioral assessment in open field, rotarod, light‐dark box, elevated plus maze and tail suspension test. Statistical analysis was performed by ANOVA one way and the means were considered significantly different when p<0.05. According to our results, the programmed animals had less time of immobility in tail suspension test (D‐fen 3mg/kg: 64.89±6.07; D‐Fen 1mg/kg: 94.15±9.67 vs. control: 130.6±13.26, p<0.001) and less time spent walking on rotarod (D‐fen 3mg/kg: 17.55±7.32; D‐Fen 1mg/kg: 22.75±7.90 vs. control: 189,7±52,33, p<0.001). In the dark light box test, the animals treated with D‐fen 3mg/kg had less time in the light side than the other groups (D‐fen 3mg/kg: 94,56±8.81 vs. D‐Fen 1mg/kg: 121.7±3.43; control: 133.9±8.01, p<0.01). These findings suggest that programming with D‐fenfluramine during the neonatal period alters neural circuits involved with coordination, anxiety and depression‐like behaviors in adults.Support: FAPERJ & CNPq.