Neonatal D-fenfluramine treatment promotes long-term behavioral changes in adult mice.

Autor: Laureano-Melo R; Multicenter and Regular Graduate Program in Physiological Sciences, Department of Physiological Sciences, Institute of Biology, Universidade Federal Rural do Rio de Janeiro, Seropedica, Brazil.; Behavioral Physiopharmacology Laboratory, Barra Mansa Center University, Rio de Janeiro, Brazil., Dos-Santos RC; Multicenter and Regular Graduate Program in Physiological Sciences, Department of Physiological Sciences, Institute of Biology, Universidade Federal Rural do Rio de Janeiro, Seropedica, Brazil., da Conceição RR; Molecular and Translational Endocrinology Laboratory, Department of Medicine, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil., de Souza JS; Molecular and Translational Endocrinology Laboratory, Department of Medicine, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil., da Silva Almeida C; Multicenter and Regular Graduate Program in Physiological Sciences, Department of Physiological Sciences, Institute of Biology, Universidade Federal Rural do Rio de Janeiro, Seropedica, Brazil., Reis LC; Multicenter and Regular Graduate Program in Physiological Sciences, Department of Physiological Sciences, Institute of Biology, Universidade Federal Rural do Rio de Janeiro, Seropedica, Brazil., Marinho BG; Multicenter and Regular Graduate Program in Physiological Sciences, Department of Physiological Sciences, Institute of Biology, Universidade Federal Rural do Rio de Janeiro, Seropedica, Brazil., Giannocco G; Molecular and Translational Endocrinology Laboratory, Department of Medicine, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil., Ahmed RG; Division of Anatomy and Embryology, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt., da Silva Côrtes W; Multicenter and Regular Graduate Program in Physiological Sciences, Department of Physiological Sciences, Institute of Biology, Universidade Federal Rural do Rio de Janeiro, Seropedica, Brazil.
Jazyk: angličtina
Zdroj: International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience [Int J Dev Neurosci] 2022 Oct; Vol. 82 (6), pp. 486-498. Date of Electronic Publication: 2022 Jun 29.
DOI: 10.1002/jdn.10204
Abstrakt: Serotonin exerts a significant role in the mammalian central nervous system embryogenesis and brain ontogeny. Therefore, we investigate the effect of neonatal treatment of d-fenfluramine (d-FEN), a serotonin (5-HT) releaser, on the behavioral expression of adult male Swiss mice. For this purpose, we divided pregnant female Swiss mice into two groups (n = 6 each and ~35 g). Their offspring were treated with d-FEN (3 mg/kg, s.c.) from postnatal days (PND) 5 to 20. At PND 21, one male puppy of each litter was euthanized; the midbrain and the hippocampus were dissected for RNA analysis. At PND 70, the male offspring underwent a behavioral assessment in the open field, elevated plus-maze, light-dark box, tail suspension, and rotarod test. The programmed animals had a decrease in 5HT1a, serotonin transporter (SERT), and brain-derived neurotrophic factor (BDNF) expression in the mesencephalic raphe region. Alternatively, there was a reduction only in the tryptophan hydroxylase (TPH2) and BDNF expression in the hippocampus. In the light-dark box test, offspring of the treated group had higher latency to light and less time on the light side than the control. Also, it was observed less time of immobility in the tail suspension test. We also observed low motor skill learning in the rotarod test. These findings suggest that programming with d-FEN during the neonatal period alters a mesencephalic and hippocampal serotonergic system, promoting anxiety, antidepressant behavior, low coordination, and motor learning in adults.
(© 2022 International Society for Developmental Neuroscience.)
Databáze: MEDLINE
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