Perinatal fluoxetine treatment promotes long-term behavioral changes in adult mice

Author(s)

Laureano-Melo, Roberto ^{[1, 2]} ; Dos-Santos, Raoni Conceicao ^[1] ; da Conceicao, Rodrigo Rodrigues ^[3] ; de Souza, Janaina Sena ^[3] ; Lau, Raphael da Silva ^[1] ; Souza Silva, Samantha da Silva ^[1] ; Marinho, Bruno Guimaraes ^[1] ; Giannocco, Gisele ^[3] ; Ahmed, R. G. ^[4] ; Cortes, Wellington da Silva ^[1]

Affiliation

^[1] Univ Fed Rural Rio de Janeiro, Multictr Grad Program Physiol Sci, Inst Hlth & Biol Sci, Dept Physiol Sci, Seropedica - Brazil

^[2] Barra Mansa Univ Ctr, Dept Vet Med, Rio De Janeiro - Brazil

^[3] Univ Fed Sao Paulo, Dept Med, Mol & Translat Endocrinol Lab, Sao Paulo, SP - Brazil

^[4] Beni Suef Univ, Fac Sci, Zool Dept, Div Anat & Embryol, Bani Suwayf - Egypt

• Document type: Journal article
• Source: METABOLIC BRAIN DISEASE; v. 35, n. 8 AUG 2020.
• Web of Science Citations: 0

Abstract

Serotonin exerts a significant role in the mammalian central nervous system embryogenesis and brain ontogeny. Therefore, we investigate the effect of perinatal fluoxetine (FLX), a selective serotonin reuptake inhibitor, administration on the behavioral expression of adult male Swiss mice. For this purpose, two groups (n = 6 each, and similar to 35 g) of pregnant female Swiss mice were mated. Their offspring were treated with FLX (10 mg/Kg, s.c.) from postnatal day (PND) 5 to 15. At PND 16, one male puppy of each litter was euthanized, and the hippocampus was dissected for RNA analysis. At 70 days of life, the male offspring underwent a behavioral assessment in the open field, object recognition task, light-dark box, tail suspension and rotarod test. According to our results, the programmed animals had a decrease in TPH2, 5HT1a, SERT, BDNF, and LMX1B expression. Also, it was observed less time of immobility in tail suspension test and higher grooming time in the open field test. In the light-dark box test, the FLX-treated offspring had less time in the light side than control. We also observed a low cognitive performance in the object recognition task and poor motor skill learning in the rotarod test. These findings suggest that programming with FLX during the neonatal period alters a hippocampal serotonergic system, promoting anxiety and antidepressant behavior in adults, as well as a low mnemonic capacity. (AU)

• FAPESP's process: 18/22763-0 - Ancient DNA, bioengineering and brain "organoids": study of thyroid hormone homeostasis and Alzheimer's Disease markers in NOVA1 gene CRISPR edited stem cells
• Grantee: Janaína Sena de Souza
• Support type: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 17/07053-3 - Effect of thyroid hormone on the brain of 3xTg-AD mice, model of Alzheimer's Disease, on glucose and cholesterol metabolism
• Grantee: Janaína Sena de Souza
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 17/23169-1 - Thyroid hormones action on 3xTg-AD (APPswe, PS1m146v, tauP301L) Alzheimer Disease´s mice model.
• Grantee: Gisele Giannocco
• Support type: Regular Research Grants