Fig 1: Characterization of the neuroendocrine effects of the chronic stress paradigm. a Schematic diagram of experimental design. b Body weight was recorded before the beginning and at the end of the chronic stress procedure. Chronically stressed mice gain less body weight than unstressed control animals. C: n = 18, CS: n = 17. Unpaired t test. t = 5.262, ***p < 0.001. c, d Chronic stress increases the weight of the adrenal glands. C: n = 18, CS: n = 17, AS: n = 10. One-way ANOVA F(2,42) = 40.14, p < 0.001 with Tukey’s multiple comparison test: ***p < 0.001 CS versus C, #p < 0.001 CS versus AS. e Corticosterone plasma levels were measured at the beginning of the light cycle. C: n = 18, CS: n = 17, AS: n = 10. One-way ANOVA F(2,42) = 26.20, p < 0.001 with Tukey’s multiple comparison test: *p < 0.05 CS versus C, ***p < 0.001 AS versus C, #p < 0.001 CS versus AS. f Hypothalamic mRNA transcription of genes associated with corticosteroid signaling. Nr3c1, nuclear receptor subfamily 3 group C member 1. Nr3c2, nuclear receptor subfamily 3 group C member 2. Fkbp4, FK506 binding protein 4. Fkbp5, FK506 binding protein 5. Crh, corticotropin releasing hormone. Relative mRNA expression is reported as the value normalized to tripeptidyl peptidase 2 (Tpp2) for each sample. C: n = 8, CS: n = 9. Mann-Whitney U test. Nr3c1: U = 27, p = 0.423. Fkbp5: U = 12, *p < 0.05. Crh: U = 14, *p < 0.05. Unpaired t test. Nr3c2: t = 1.016, p = 0.326. Fkbp4: t = 1.214, p = 0.244. g Representative Western blots of GR and FKBP5 protein expression in hypothalamic homogenates. GR, glucocorticoid receptor. FKBP5, FK506 binding protein 51. ACTB, β-actin. h Densitometric analysis. Values were normalized to β-actin. C: n = 8, CS: n = 9. Unpaired t test. GR: t = 0.029, p = 0.977. FKBP5: t = 2.173, *p < 0.05. C, unstressed control mice. CS, chronically stressed mice. AS, acutely stressed mice