Psychogenic or Physical Stress Produce a Similar Manner of Modulation on the Pineal Gland in Rats

Introduction: We have previously shown that perfusion of pineal glands with concentration of corticosterone, which mimics activation of the hypothalamic-pituitary-adrenal (HPA) axis, leads to an increase in nocturnal melatonin surge. In cultured pineal glands we observed a dual effect of corticosterone, it inhibits melatonin production when both alfa and beta adrenoceptors are stimulated, while it potentiates melatonin output when only beta-adrenoceptors are activated. Glucocorticoid receptors and inhibition of the nuclear transcription factor kappa B (NFKB) mediate glucocorticoid effect in the pineal gland. Here, our aim was to test whether heightened corticosterone by restraint (psychogenic stress) or cold exposure (physical stress) could change nocturnal melatonin surge in rats. Methods: Male Wistar rats (12:12 L/D cycle, aged 3-4 months). Pineal content of N-acetylserotonin (NAS) and melatonin (MEL) from rat killed at ZT 18-20 were quantified by HPLC (ng/pineal) into 3 groups (5/group): control with individually housed in cage (CTRL), restraint in an apparatus (REST), and cold in a refrigerator (5.0 ± 1.0 °C) (COLD), for 0.5 or 2h. Plasma level of corticosterone (ng/mL) and TNF (pg/mL) were determined into 3 groups: naïve, non-experimentally manipulated euthanized at ZT11 (N Day) or at ZT14 (N Night), restraint and cold for 2h euthanized at 0, 10, 30, 60 and 120 min after stress. In both studies, gastric ulcers were determined after euthanasia. The regression of the data was tested by two-way ANOVA. Results: REST and COLD did not induced gastric ulcer neither sudoresis. Pineal NAS did not modify in manipulated groups in relation to control groups. Pineal MEL doubled from REST 0.5 (1.7±0.2) to REST 2.0 (3.3±0.6), and from COLD 0.5 (1.9±0.5) to COLD 2.0 (3.4±0.8), while no regression on time was detected for CTRL animals. No level of TNF was observed, while corticosterone increased more than 2-fold just after 2h of restraint or cold stress, returning naïve values in 30 min (148.8±32.5) following an exponential curve. Conclusion: Our data clearly show that the increase in corticosterone, due to activation of the HPA axis, leads to an increase in nocturnal melatonin, without changing the production of NAS. Taking into account that we observed no gastric ulcer or other sign of exacerbated sympathetic activation, our data corroborates to the hypothesis that under a normal sympathetic output, enhancement of corticosterone promotes an increase nocturnal melatonin surge in rats. Support: CAPES, CNPq and FAPESP. Publication History Article published online: 16 June 2026 © 2009. Brazilian Sleep Academy. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/) Thieme Revinter Publicações Ltda. Rua Rego Freitas, 175, loja 1, República, São Paulo, SP, CEP 01220-010, Brazil