Chronic restraint stress induces serotonin transporter expression in the rat adrenal glands.

Chronic restraint stress (CRS) magnifies restraint-induced corticosterone secretion through a mechanism involving increased adrenocortical 5-HT content and turnover. We analysed the impact of CRS on serotonin transporter (SERT) expression and distribution in rat adrenal glands. Male Wistar rats were submitted to CRS (20 min/day) or undisturbed control conditions for 14 days. Exposure to CRS induced a remarkable increase in SERT-like immunoreactivity in the adrenal cortex, which closely matched that of chromogranin A immunostaining, along with a significant increase in SERT protein and mRNA levels in whole adrenals as determined by immunohistochemistry, Western blot and RT-PCR assays, respectively; all these CRS-induced changes occurred almost exclusively in left adrenals. Closely similar results were obtained in animals that received a 14-day chronic corticosterone treatment. These results unravel an interesting association between chronic stress exposure and SERT expression in adrenocortical chromogranin A-positive cells, which seems to be a glucocorticoid-dependent phenomenon.

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

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.