Lithium-induced malaise does not interfere with adaptation of the hypothalamic-pituitary-adrenal axis to stress

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 75; pp. 77 - 83
• Main Authors: Sanchís-Ollé, Maria, Ortega-Sánchez, Juan A., Belda, Xavier, Gagliano, Humberto, Nadal, Roser, Armario, Antonio
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 03.04.2017
• Subjects: Adaptation; Adaptation, Physiological - drug effects; Adrenocorticotropic Hormone - blood; Animals; Antimanic Agents - adverse effects; Body Weight - drug effects; Conditioned taste aversion; Corticosterone - blood; Disease Models, Animal; Hypothalamic-pituitary-adrenal axis; Hypothalamo-Hypophyseal System - drug effects; Immobilization stress; Lithium chloride; Lithium Chloride - adverse effects; Male; Pituitary-Adrenal System - drug effects; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Saccharin - metabolism; Stress, Psychological - drug therapy; Stress, Psychological - metabolism; Stress-induced malaise; Time Factors; Hypothalamic-pituitary-adrenal axis; Conditioned taste aversion; Lithium chloride; Stress-induced malaise; Immobilization stress; Adaptation
• DOI: 10.1016/j.pnpbp.2017.01.006
• ISSN: 0278-5846

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. •Lithium chloride (ip) causes conditioned taste aversion (CTA) for saccharin.•Lithium weakly activates the hypothalamic-pituitary-adrenal (HPA) axis.•Immobilization (IMO) stress causes strong HPA activation and CTA.•Lithium given during a first IMO does not affect HPA adaptation to the same stressor.