title: Lithium-induced malaise does not interfere with adaptation of the hypothalamic-pituitary-adrenal axis to stress.
abstract: We have recently demonstrated that adaptation of the hypothalamic-pituitary-adrenal (HPA) axis to repeated exposure to a stressor does not follow the rules of habituation and can be fully expressed after a single experience with severe stressors. In the present work we tested the hypothesis that adaptation could be impaired if animals experience malaise during initial exposure to the stressor. To this end, animals were allowed to drink saccharin for 30min before being exposed for 3h to immobilization on boards (IMO), a severe stressor; then they were given either saline or lithium ip after the first hour of IMO. Stress-naïve rats followed exactly the same procedure except IMO. Exposure to IMO caused a strong activation of the HPA axis whereas the effect of lithium was modest. Both IMO and lithium administration resulted in conditioned taste aversion to saccharin when evaluated 4days later. When all animals were exposed to IMO 6days later, reduced HPA response and less impact on body weight was observed in the two groups previously exposed to IMO as compared with stress-naïve rats. Therefore, lithium administration during the first IMO exposure did not affect adaptation of the HPA axis and weight gain. These results indicate that malaise per se only weakly activated the HPA axis and argue against the hypothesis that signs of physical malaise during exposure to the stressor could impair HPA adaptation.
authors.affiliation: Institut de Neurociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain; Red de trastornos adictivos and CIBERSAM, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain; Animal Physiology Unit, School of Biosciences, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Sanchís-Ollé
authors.affiliation: Institut de Neurociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain; Red de trastornos adictivos and CIBERSAM, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain; Animal Physiology Unit, School of Biosciences, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Ortega-Sánchez
authors.affiliation: Institut de Neurociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain; Red de trastornos adictivos and CIBERSAM, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain; Animal Physiology Unit, School of Biosciences, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Belda
authors.affiliation: Institut de Neurociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain; Red de trastornos adictivos and CIBERSAM, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain; Animal Physiology Unit, School of Biosciences, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain.
authors.forename: Humberto
authors.initials: H
authors.lastname: Gagliano
authors.affiliation: Institut de Neurociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain; Red de trastornos adictivos and CIBERSAM, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain; Psychobiology Unit, School of Psychology, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain.
authors.forename: Roser
authors.initials: R
authors.lastname: Nadal
authors.affiliation: Institut de Neurociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain; Red de trastornos adictivos and CIBERSAM, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain; Animal Physiology Unit, School of Biosciences, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain. Electronic address: antonio.armario@uab.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Armario
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D018692:Antimanic Agents / Q000009:adverse effects*; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D018021:Lithium Chloride / Q000009:adverse effects*; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012439:Saccharin / Q000378:metabolism; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism; D013997:Time Factors
chemical_list: D018692:Antimanic Agents; D000324:Adrenocorticotropic Hormone; D012439:Saccharin; D018021:Lithium Chloride; D003345:Corticosterone
keywords: Adaptation; Conditioned taste aversion; Hypothalamic-pituitary-adrenal axis; Immobilization stress; Lithium chloride; Stress-induced malaise