title: Effects of intracerebroventricular administered fluoxetine on cardio-ventilatory functions in rainbow trout (Oncorhynchus mykiss).
abstract: Fluoxetine (FLX) is a selective serotonin (5-HT) reuptake inhibitor present in the aquatic environment which is known to bioconcentrate in the brains of exposed fish. FLX acts as a disruptor of various neuroendocrine functions in the brain, but nothing is known about the possible consequence of FLX exposure on the cardio-ventilatory system in fish. Here we undertook to investigate the central actions of FLX on ventilatory and cardiovascular function in unanesthetized rainbow trout (Oncorhynchus mykiss). Intracerebroventricular (ICV) injection of FLX (dosed between 5 and 25 μg) resulted in a significantly elevated total ventilation (VTOT), with a maximum hyperventilation of +176% (at a dose of 25μg) compared with vehicle injected controls. This increase was due to an increase in ventilatory amplitude (VAMP: +126%) with minor effects on ventilatory frequency. The highest dose of FLX (25 μg) produced a significant increase in mean dorsal aortic blood pressure (PDA: +20%) without effects on heart rate (ƒH). In comparison, intra-arterial injections of FLX (500-2,500 μg) had no effect on ventilation but the highest doses increased both PDA and ƒH. The ICV and IA cardio-ventilatory effects of FLX were very similar to those previously observed following injections of 5-HT, indicating that FLX probably acts via stimulating endogenous 5-HT activity through inhibition of 5-HT transporter(s). Our results demonstrate for the first time in fish that FLX administered within the brain exerts potent stimulatory effects on ventilation and blood pressure increase. The doses of FLX given to fish in our study are higher than the brain concentrations of FLX in fish that result from acute exposure to FLX through the water. Nonetheless, our results indicate possible disrupting action of long term exposure to FLX discharged into the environment on central target sites sensitive to 5-HT involved in cardio-ventilatory control.
authors.affiliation: Université Européenne de Bretagne, Université de Brest, INSERM U1101, Laboratoire de Traitement de l'Information Médicale, Laboratoire de Neurophysiologie, SFR ScInBioS, Faculté de Médecine et des Sciences de la Santé, CHU de Brest, 22 Avenue Camille Desmoulins, CS 93837, 29238 Brest Cedex 3, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Kermorgant
authors.affiliation: Université Européenne de Bretagne, Université de Brest, INSERM U1101, Laboratoire de Traitement de l'Information Médicale, Laboratoire de Neurophysiologie, SFR ScInBioS, Faculté de Médecine et des Sciences de la Santé, CHU de Brest, 22 Avenue Camille Desmoulins, CS 93837, 29238 Brest Cedex 3, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lancien
authors.affiliation: Université Européenne de Bretagne, Université de Brest, INSERM U1101, Laboratoire de Traitement de l'Information Médicale, Laboratoire de Neurophysiologie, SFR ScInBioS, Faculté de Médecine et des Sciences de la Santé, CHU de Brest, 22 Avenue Camille Desmoulins, CS 93837, 29238 Brest Cedex 3, France.
authors.forename: Nagi
authors.initials: N
authors.lastname: Mimassi
authors.affiliation: Biosciences, University of Exeter, Exeter, United Kingdom.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Tyler
authors.affiliation: Université Européenne de Bretagne, Université de Brest, INSERM U1101, Laboratoire de Traitement de l'Information Médicale, Laboratoire de Neurophysiologie, SFR ScInBioS, Faculté de Médecine et des Sciences de la Santé, CHU de Brest, 22 Avenue Camille Desmoulins, CS 93837, 29238 Brest Cedex 3, France. Electronic address: Jean-Claude.LeMevel@univ-brest.fr.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Le Mével
mesh_terms: D000758:Anesthesia; D000818:Animals; D005473:Fluoxetine / Q000008:administration & dosage* / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D007269:Injections, Intra-Arterial; D007276:Injections, Intraventricular; D017686:Oncorhynchus mykiss / Q000502:physiology*; D012119:Respiration / Q000187:drug effects*; D013997:Time Factors
chemical_list: D005473:Fluoxetine
keywords: Central fluoxetine; Hypertension; Hyperventilation; Intracerebroventricular injection; Serotonin; Teleost