title: Exogenous oxytocin reduces signs of sickness behavior and modifies heart rate fluctuations of endotoxemic rats.
abstract: Besides the well-known roles of oxytocin on birth, maternal bonding, and lactation, recent evidence shows that this hypothalamic hormone possesses cardioprotective, anti-inflammatory and parasympathetic neuromodulation properties. In this study, we explore the heart rate fluctuations (HRF) in an endotoxemic rodent model that was accompanied by the administration of exogenous oxytocin. The assessment of HRF has been widely used as an indirect measure of the cardiac autonomic function. In this context, adult male Dark Agouti rats were equipped with a telemetric transmitter to continuously and remotely measure the electrocardiogram, temperature, and locomotion. In a between-subjects experimental design, rats received the following peripheral treatment: saline solution as a vehicle (V); lipopolysaccharide (LPS); oxytocin (Ox); lipopolysaccharide + oxytocin (LPS+Ox). Linear and non-linear parameters of HRF were estimated starting 3h before to 24h after treatments. Our results showed that exogenous oxytocin does not modify by itself the HRF of oxytocin-treated rats in comparison to vehicle-treated rats. However, in animals undergoing endotoxemia it: a) provokes a less anticorrelated pattern in HRF, b) decreased mean heart rate, c) moderated the magnitude and duration of the LPS-induced hyperthermia, and d) increased locomotion, up to 6h after the LPS injection. The less anticorrelated pattern in the HRF and decreased mean heart rate may reflect a cardiac pacemaker coupling with cholinergic influences mediated by oxytocin during LPS-induced endotoxemia. Finally, the anti-lethargic and long-term temperature moderating effects of the administration of oxytocin during endotoxemia could be a consequence of the systemic anti-inflammatory properties of oxytocin.
authors.affiliation: Metropolitan University (UAM), Campus Iztapalapa, Basic Sciences and Engineering Division, Mexico City 09340, Mexico.
authors.forename: José Javier
authors.initials: JJ
authors.lastname: Reyes-Lagos
authors.affiliation: University of Duisburg-Essen, University Hospital Essen, Institute of Medical Psychology and Behavioral Immunobiology, Essen 45122, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hadamitzky
authors.affiliation: Metropolitan University (UAM), Campus Iztapalapa, Basic Sciences and Engineering Division, Mexico City 09340, Mexico.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Peña-Castillo
authors.affiliation: Metropolitan University (UAM), Campus Iztapalapa, Basic Sciences and Engineering Division, Mexico City 09340, Mexico.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Echeverría
authors.affiliation: University of Duisburg-Essen, University Hospital Essen, Institute of Medical Psychology and Behavioral Immunobiology, Essen 45122, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Bösche
authors.affiliation: University of Duisburg-Essen, University Hospital Essen, Institute of Medical Psychology and Behavioral Immunobiology, Essen 45122, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Lückemann
authors.affiliation: University of Duisburg-Essen, University Hospital Essen, Institute of Medical Psychology and Behavioral Immunobiology, Essen 45122, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Schedlowski
authors.affiliation: Metropolitan University (UAM), Campus Lerma, Biological and Health Sciences Division, Lerma 52005, Mexico; Leiden University, Faculty of Social and Behavioral Sciences, Health, Medical and Neuropsychology Unit, Leiden, 2333, AK, The Netherlands. Electronic address: g.pacheco@correo.ler.uam.mx.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Pacheco-López
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001831:Body Temperature / Q000187:drug effects; D004195:Disease Models, Animal; D004562:Electrocardiography; D019446:Endotoxemia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D004731:Endotoxins / Q000633:toxicity; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D055809:Illness Behavior / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D010121:Oxytocin / Q000627:therapeutic use*; D051381:Rats; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D010121:Oxytocin
keywords: Anti-inflammatory cholinergic pathway; Autonomic activity; Heart rate variability; LPS; Oxytocin; Sickness behavior