Pre-hatching fluoxetine-induced neurochemical, neurodevelopmental, and immunological changes in newly hatched cuttlefish

Flavie Bidel, Carole Di Poi, Boudjema Imarazene, Noussithé Koueta, Hélène Budzinski, Pierre Van Delft, Cécile Bellanger, Christelle Jozet-Alves

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14 Scopus citations


Embryonic and early postembryonic development of the cuttlefish Sepia officinalis (a cephalopod mollusk) occurs in coastal waters, an environment subject to considerable pressure from xenobiotic pollutants such as pharmaceutical residues. Given the role of serotonin in brain development and its interaction with neurodevelopmental functions, this study focused on fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI, antidepressant). The goal was to determine the effects of subchronic waterborne FLX exposure (1 and 10 μg L−1) during the last 15 days of embryonic development on neurochemical, neurodevelopmental, behavioral, and immunological endpoints at hatching. Our results showed for the first time that organic contaminants, such as FLX, could pass through the eggshell during embryonic development, leading to a substantial accumulation of this molecule in hatchlings. We also found that FLX embryonic exposure (1 and 10 μg L−1) (1) modulated dopaminergic but not serotonergic neurotransmission, (2) decreased cell proliferation in key brain structures for cognitive and visual processing, (3) did not induce a conspicuous change in camouflage quality, and (4) decreased lysozyme activity. In the long term, these alterations observed during a critical period of development may impair complex behaviors of the juvenile cuttlefish and thus lead to a decrease in their survival. Finally, we suggest a different mode of action by FLX between vertebrate and non-vertebrate species and raise questions regarding the vulnerability of early life stages of cuttlefish to the pharmaceutical contamination found in coastal waters.

Original languageEnglish (US)
Pages (from-to)5030-5045
Number of pages16
JournalEnvironmental Science and Pollution Research
Issue number6
StatePublished - Mar 1 2016
Externally publishedYes

Bibliographical note

Funding Information:
This work is a contribution to the Pharm@Ecotox project funded by the French National Research Agency (ANR, fr: Agence Nationale de la Recherche). This research was also supported by a post-doctoral grant from the Université de Caen Basse-Normandie (France) to C. Di Poï and a doctoral grant from the Conseil Régional de Basse-Normandie (France) to F. Bidel. The authors gratefully acknowledge Nadège Naud and Céline Thomasse for their work in the neurobiological study, Charles Lepabic for his help in the immunological study, Caitlin O’Brien for editing the English in this manuscript, and the staff of the Centre de Recherches en Environnement Côtier (Luc-sur-Mer, France) for egg collection and technical assistance.

Publisher Copyright:
© 2015, Springer-Verlag Berlin Heidelberg.


  • Bioconcentration
  • Brain maturation
  • Camouflage
  • Cell proliferation
  • Cephalopods
  • Immune system
  • Monoamines
  • Selective serotonin reuptake inhibitor (SSRI)


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