Validation of the long-term assessment of hypothalamic-pituitary-adrenal activity in rats using hair corticosterone as a biomarker.
The evaluation of chronic activity of the hypothalamic-pituitary-adrenal (HPA) axis is critical for determining the impact of chronic stressful situations. However, current methods have important limitations. The potential use of hair glucocorticoids as a noninvasive retrospective biomarker of long-term HPA activity is gaining acceptance in humans and wild animals. However, there is no study examining hair corticosterone (HC) in laboratory animals. The present study validates a method for measuring HC in rats and demonstrates that it properly reflects chronic HPA activity. The HC concentration was similar in male and female rats, despite higher total plasma corticosterone levels in females, tentatively suggesting that it reflects free rather than total plasma corticosterone. Exposure of male rats to 2 different chronic stress protocols (chronic immobilization and chronic unpredictable stress) resulted in similarly higher HC levels compared to controls (1.8-fold). HC also increased after a mild chronic stressor (30 min daily restraint). Chronic administration of 2 different doses of a long-acting ACTH preparation dramatically increased HC (3.1- and 21.5-fold, respectively), demonstrating that a ceiling effect in HC accumulation is unlikely under other more natural conditions. Finally, adrenalectomy significantly reduced HC. In conclusion, HC measurement in rats appears appropriate to evaluate integrated chronic changes in circulating corticosterone.
*Department of Veterinary Medical Sciences, Animal Physiology Unit, Faculty of Veterinary Medicine, University of Bologna, 40064 Ozzano dell'Emilia, Bologna, Italy; Unitat de Fisiologia Animal (Facultat de Veterinaria), Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain; Unitat de Fisiologia Animal (Facultat de Biociències), Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain; Institut de Neurociències, Universitat Autonòma de Barcelona, 08193 Bellaterra, Barcelona, Spain; and Red de trastornos adictivos (RTA), Instituto de Salud Carlos III, Madrid, Spain.
Fabrizio
F
Scorrano
*Department of Veterinary Medical Sciences, Animal Physiology Unit, Faculty of Veterinary Medicine, University of Bologna, 40064 Ozzano dell'Emilia, Bologna, Italy; Unitat de Fisiologia Animal (Facultat de Veterinaria), Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain; Unitat de Fisiologia Animal (Facultat de Biociències), Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain; Institut de Neurociències, Universitat Autonòma de Barcelona, 08193 Bellaterra, Barcelona, Spain; and Red de trastornos adictivos (RTA), Instituto de Salud Carlos III, Madrid, Spain.
Javier
J
Carrasco
*Department of Veterinary Medical Sciences, Animal Physiology Unit, Faculty of Veterinary Medicine, University of Bologna, 40064 Ozzano dell'Emilia, Bologna, Italy; Unitat de Fisiologia Animal (Facultat de Veterinaria), Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain; Unitat de Fisiologia Animal (Facultat de Biociències), Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain; Institut de Neurociències, Universitat Autonòma de Barcelona, 08193 Bellaterra, Barcelona, Spain; and Red de trastornos adictivos (RTA), Instituto de Salud Carlos III, Madrid, Spain.
Jordi
J
Pastor-Ciurana
*Department of Veterinary Medical Sciences, Animal Physiology Unit, Faculty of Veterinary Medicine, University of Bologna, 40064 Ozzano dell'Emilia, Bologna, Italy; Unitat de Fisiologia Animal (Facultat de Veterinaria), Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain; Unitat de Fisiologia Animal (Facultat de Biociències), Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain; Institut de Neurociències, Universitat Autonòma de Barcelona, 08193 Bellaterra, Barcelona, Spain; and Red de trastornos adictivos (RTA), Instituto de Salud Carlos III, Madrid, Spain.
Xavier
X
Belda
*Department of Veterinary Medical Sciences, Animal Physiology Unit, Faculty of Veterinary Medicine, University of Bologna, 40064 Ozzano dell'Emilia, Bologna, Italy; Unitat de Fisiologia Animal (Facultat de Veterinaria), Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain; Unitat de Fisiologia Animal (Facultat de Biociències), Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain; Institut de Neurociències, Universitat Autonòma de Barcelona, 08193 Bellaterra, Barcelona, Spain; and Red de trastornos adictivos (RTA), Instituto de Salud Carlos III, Madrid, Spain.
Alicia
A
Rami-Bastante
*Department of Veterinary Medical Sciences, Animal Physiology Unit, Faculty of Veterinary Medicine, University of Bologna, 40064 Ozzano dell'Emilia, Bologna, Italy; Unitat de Fisiologia Animal (Facultat de Veterinaria), Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain; Unitat de Fisiologia Animal (Facultat de Biociències), Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain; Institut de Neurociències, Universitat Autonòma de Barcelona, 08193 Bellaterra, Barcelona, Spain; and Red de trastornos adictivos (RTA), Instituto de Salud Carlos III, Madrid, Spain.
Maria Laura
ML
Bacci
*Department of Veterinary Medical Sciences, Animal Physiology Unit, Faculty of Veterinary Medicine, University of Bologna, 40064 Ozzano dell'Emilia, Bologna, Italy; Unitat de Fisiologia Animal (Facultat de Veterinaria), Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain; Unitat de Fisiologia Animal (Facultat de Biociències), Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain; Institut de Neurociències, Universitat Autonòma de Barcelona, 08193 Bellaterra, Barcelona, Spain; and Red de trastornos adictivos (RTA), Instituto de Salud Carlos III, Madrid, Spain antonio.armario@uab.es.
Antonio
A
Armario
D000315:Adrenalectomy; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D003345:Corticosterone / Q000097:blood*; D005260:Female; D006197:Hair / Q000737:chemistry*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000150:complications*
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D003345:Corticosterone
ACTH; chronic immobilization; chronic unpredictable stress; glucocorticoids