title: Sensitization of restraint-induced corticosterone secretion after chronic restraint in rats: involvement of 5-HT₇ receptors.
abstract: Serotonin (5-HT) modulates the hypothalamic-pituitary-adrenal (HPA) axis response to stress. We examined the effect of chronic restraint stress (CRS; 20 min/day) as compared to control (CTRL) conditions for 14 days, on: 1) restraint-induced ACTH and corticosterone (CORT) secretion in rats pretreated with vehicle or SB-656104 (a 5-HT₇ receptor antagonist); 2) 5-HT₇ receptor-like immunoreactivity (5-HT₇-LI) and protein in the hypothalamic paraventricular nucleus (PVN) and adrenal glands (AG); 3) baseline levels of 5-HT and 5-hydroxyindolacetic acid (5-HIAA), and 5-HIAA/5-HT ratio in PVN and AG; and 4) 5-HT-like immunoreactivity (5-HT-LI) in AG and tryptophan hydroxylase (TPH) protein in PVN and AG. On day 15, animals were subdivided into Treatment and No treatment groups. Treatment animals received an i.p. injection of vehicle or SB-656104; No Treatment animals received no injection. Sixty min later, Treatment animals were either decapitated with no further stress (0 min) or submitted to acute restraint (10, 30, 60 or 120 min); hormone serum levels were measured. No Treatment animals were employed for the rest of measurements. CRS decreased body weight gain and increased adrenal weight. In CTRL animals, acute restraint increased ACTH and CORT secretion in a time of restraint-dependent manner; both responses were inhibited by SB-656104. Exposure to CRS abolished ACTH but magnified CORT responses to restraint as compared to CTRL conditions; SB-656104 had no effect on ACTH levels but significantly inhibited sensitized CORT responses. In CTRL animals, 5-HT₇-LI was detected in magnocellular and parvocellular subdivisions of PVN and sparsely in adrenal cortex. Exposure to CRS decreased 5-HT₇-LI and protein in the PVN, but increased 5-HT₇-LI in the adrenal cortex and protein in whole AG. Higher 5-HT and 5-HIAA levels were detected in PVN and AG from CRS animals but 5-HIAA/5-HT ratio increased in AG only. Finally, whereas 5-HT-LI was sparsely observed in the adrenal cortex of CTRL animals, it strongly increased in the adrenal cortex of CRS animals. No TPH protein was detected in AG from both animal groups. Results suggest that CRS promotes endocrine disruption involving decreased ACTH and sensitized CORT responses to acute restraint. This phenomenon may be associated with increased function and expression of 5-HT₇ receptors as well as 5-HT turnover in AG.
authors.affiliation: Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Apartado Postal 14-740, Zacatenco 07000, Mexico City, Mexico.
authors.forename: Brenda B
authors.initials: BB
authors.lastname: García-Iglesias
authors.forename: María E
authors.initials: ME
authors.lastname: Mendoza-Garrido
authors.forename: Gabriel
authors.initials: G
authors.lastname: Gutiérrez-Ospina
authors.forename: Claudia
authors.initials: C
authors.lastname: Rangel-Barajas
authors.forename: Martha
authors.initials: M
authors.lastname: Noyola-Díaz
authors.forename: José A
authors.initials: JA
authors.lastname: Terrón
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism*; D012149:Restraint, Physical; D012702:Serotonin Antagonists / Q000494:pharmacology; D013312:Stress, Physiological / Q000187:drug effects; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C522380:5-HT(7) receptor, rat; D009419:Nerve Tissue Proteins; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone
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