Effect of chronic corticosterone treatment on expression and distribution of serotonin 5-HT7 receptors in rat adrenal glands

Can J Physiol Pharmacol. 2019 Oct;97(10):924-931. doi: 10.1139/cjpp-2019-0080. Epub 2019 May 27.

Abstract

Sensitized stress-induced corticosterone (CORT) secretion in chronically stressed rats involves 5-HT7 receptor activation. The effect of 14-day chronic CORT and vehicle (VEH) administration on 5-HT7 receptor expression in adrenal glands, adrenal 5-HT content, and adrenocorticotropic hormone and CORT secretion was analysed. On day 15, VEH- and CORT-treated animals were perfused or decapitated without stress exposure (0 min) or after 10 and 30 min of restraint for collection of trunk blood and tissues. 5-HT7 receptor-like immunoreactivity (5-HT7R-LI), 5-HT7 receptor protein, and mRNA levels were determined by immunohistochemistry, Western blot, and reverse transcription polymerase chain reaction assays, respectively; 5-HT levels and hormones were quantified using HPLC and ELISA kits, respectively. An undisturbed control group was included for most experimental comparisons. Chronic CORT strongly increased 5-HT7R-LI in the outer adrenal cortex, as well as 5-HT7 receptor protein and mRNA in whole adrenal glands; adrenal 5-HT content also increased in these animals. Decreased adrenocorticotropic hormone and CORT secretion at 30 min of restraint occurred in CORT-treated rats. The results support the notion that chronic stress-induced increase of adrenocortical 5-HT7 receptors and adrenal 5-HT content is a glucocorticoid-dependent phenomenon; the development of magnified stress-induced 5-HT7 receptor-mediated CORT responses in chronically stressed animals nevertheless likely involves additional mechanisms.

Keywords: 5-HT7 receptors; ACTH; administration à long terme de corticostérone; adrenal cortex; chronic corticosterone treatment; chronic stress; cortex surrénalien; corticotropine; récepteurs 5-HT7; stress de longue durée.

MeSH terms

  • Adrenal Glands / drug effects*
  • Adrenal Glands / metabolism
  • Adrenocorticotropic Hormone / analysis
  • Adrenocorticotropic Hormone / metabolism
  • Animals
  • Corticosterone / administration & dosage*
  • Corticosterone / metabolism
  • Disease Models, Animal
  • Humans
  • Hypothalamo-Hypophyseal System / metabolism
  • Male
  • Pituitary-Adrenal System / metabolism
  • Rats
  • Receptors, Serotonin / analysis
  • Receptors, Serotonin / metabolism*
  • Restraint, Physical / psychology
  • Serotonin / analysis
  • Serotonin / metabolism
  • Stress, Psychological / etiology
  • Stress, Psychological / metabolism*
  • Stress, Psychological / psychology

Substances

  • Receptors, Serotonin
  • serotonin 7 receptor
  • Serotonin
  • Adrenocorticotropic Hormone
  • Corticosterone