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 ~ 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.
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Acknowledgements
We thank the National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq) and Coordination of Superior Level Staff Improvement (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – CAPES) for the fellowship granted to graduate students present in this project, the Fundação de Amparo à Pesquisa do Estado de São Paulo to Janaina Sena de Souza (FAPESP, São Paulo, Brazil, processes #2017/07053-3 and #2018/22763-0) and Gisele Giannocco (FAPESP, São Paulo, Brazil, process #2017/23169-1). We also thank Antonio Vicente C. L. da Costa and Ipojucan Pereira de Souza, employers of Federal Rural University of Rio de Janeiro (UFRuralRJ).
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Laureano-Melo, R., Dos-Santos, R.C., da Conceição, R.R. et al. Perinatal fluoxetine treatment promotes long-term behavioral changes in adult mice. Metab Brain Dis 35, 1341–1351 (2020). https://doi.org/10.1007/s11011-020-00606-2
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DOI: https://doi.org/10.1007/s11011-020-00606-2