The antidepressant venlafaxine may act as a neurodevelopmental toxicant in cuttlefish (Sepia officinalis).
The Serotonin/Norepinephrine Reuptake Inhibitor (SNRI) antidepressant venlafaxine (VEN, Effexor(®)) has become one of the most common antidepressants detected in North American and European streams. Mammalian research has established that VEN exposure is associated with a range of structural, neurochemical, and functional alterations of the brain in adults and newborns. However, the neurodevelopmental effects of VEN on non-target organisms have never been investigated. The aim of our research was to decrease this gap in knowledge by characterizing the effects of VEN exposure on a cephalopod mollusk, the common cuttlefish Sepia officinalis. This species inhabits VEN-contaminated waters and possesses an unusually sophisticated brain. These characteristics render it a unique invertebrate species for studying the neurodevelopmental effects of VEN. Cuttlefish were exposed to environmentally-relevant concentrations of VEN (Measured concentrations ≈5 and 100ngL(-)(1)) or to filtered natural seawater (control) in a closed-loop system with regular water changes during the first 20days after hatching. We evaluated brain maturation as well as neurochemical changes and behavioral performances during this critical period of development. Our results show that both VEN-exposed groups exhibited a decrease in norepinephrine levels, along with a reduction in the relative number of glutamate NMDA-like receptors binding sites in the group exposed to 5ngL(-1) of VEN after 20days of exposure. Brain regional changes in cellular proliferation were observed in VEN-exposed groups in the vertical lobe (i.e. a key structure involved in cognitive processes) and in the optic lobes (i.e. main visual processing centers) in the absence of significant change in their volume. Along with these neurodevelopmental changes, 20days of exposure to 100ngL(-1) of VEN was associated with a decrease in camouflage ability. Overall, our study suggests that VEN is a neurodevelopmental toxicant in non-target aquatic organisms at environmentally-relevant concentrations.
Normandie Université, CS F-14032 Caen, France; GMPc (Groupe Mémoire et Plasticité comportementale), EA 4259, Campus Horowitz, Université de Caen Normandie, Esplanade de la Paix, CS F-14032 Caen cedex, France.
Flavie
F
Bidel
Normandie Université, CS F-14032 Caen, France; GMPc (Groupe Mémoire et Plasticité comportementale), EA 4259, Campus Horowitz, Université de Caen Normandie, Esplanade de la Paix, CS F-14032 Caen cedex, France.
Carole
C
Di Poi
EPOC (Environnements et Paléoenvironnements Océaniques et Continentaux), UMR 5805 CNRS, Laboratoire de Physico- et Toxico-Chimie de l'Environnement (LPTC), 351 crs de la Libération, F-33405 Talence, France.
Hélène
H
Budzinski
EPOC (Environnements et Paléoenvironnements Océaniques et Continentaux), UMR 5805 CNRS, Laboratoire de Physico- et Toxico-Chimie de l'Environnement (LPTC), 351 crs de la Libération, F-33405 Talence, France.
Patrick
P
Pardon
Normandie Université, CS F-14032 Caen, France; GMPc (Groupe Mémoire et Plasticité comportementale), EA 4259, Campus Horowitz, Université de Caen Normandie, Esplanade de la Paix, CS F-14032 Caen cedex, France.
William
W
Callewaert
Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, QC, H9X 2T9, Canada.
Adeline
A
Arini
Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, QC, H9X 2T9, Canada.
Niladri
N
Basu
Normandie Université, CS F-14032 Caen, France; GMPc (Groupe Mémoire et Plasticité comportementale), EA 4259, Campus Horowitz, Université de Caen Normandie, Esplanade de la Paix, CS F-14032 Caen cedex, France.
Ludovic
L
Dickel
Normandie Université, CS F-14032 Caen, France; GMPc (Groupe Mémoire et Plasticité comportementale), EA 4259, Campus Horowitz, Université de Caen Normandie, Esplanade de la Paix, CS F-14032 Caen cedex, France.
Cécile
C
Bellanger
Normandie Université, CS F-14032 Caen, France; GMPc (Groupe Mémoire et Plasticité comportementale), EA 4259, Campus Horowitz, Université de Caen Normandie, Esplanade de la Paix, CS F-14032 Caen cedex, France. Electronic address: christelle.alves@unicaen.fr.
Christelle
C
Jozet-Alves
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D049832:Decapodiformes; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D008995:Monoamine Oxidase / Q000378:metabolism; D065886:Neurodevelopmental Disorders / Q000139:chemically induced* / Q000473:pathology; D009638:Norepinephrine / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D018709:Statistics, Nonparametric; D000069470:Venlafaxine Hydrochloride / Q000633:toxicity*
D018687:Antidepressive Agents, Second-Generation; D017470:Receptors, Glutamate; D012701:Serotonin; D000069470:Venlafaxine Hydrochloride; D008995:Monoamine Oxidase; D004298:Dopamine; D009638:Norepinephrine
Brain maturation; Camouflage; Cell proliferation; Cephalopods; Monoamines; Serotonin/Norepinephrine Reuptake Inhibitor (SNRI)