Regional and subcellular changes in the concentration of 5‐hydroxytryptamine and 5‐hydroxyindoleacetic acid in the rat brain caused by hydrocortisone, DL‐α‐methyltryptophan l‐kynurenine and immobilization

Abstract

In agreement with previous findings on whole brain, the intraperitoneal injection of hydrocortisone, DL‐α‐methyltryptophan or l‐kynurenine decreased the concentrations of 5‐hydroxytryptamine (5‐HT) and 5‐hydroxyindoleacetic acid (5‐HIAA) in different regions of the rat brain. Hydrocortisone caused similar decreases in the concentrations of both 5‐HT and 5‐HIAA, suggesting decreased 5‐HT synthesis. Changes in the concentration of 5‐HIAA after hydrocortisone corresponded significantly to those after α‐methyltryptophan. Changes in the concentration of 5‐HT did not correspond, possibly due to falsely high 5‐HT values because of interfering material derived from α‐methyltryptophan. In general, kynurenine caused larger decreases in the concentration of 5‐HT than in the concentration of 5‐HIAA. In agreement with previous findings with whole brain, immobilization of rats for 5 h decreased the concentration of 5‐HT and increased that of 5‐HIAA in most brain regions. The order of the percentage decreases in the concentrations of 5‐HIAA 6 h after hydrocortisone injection was, in decreasing order: hypothalamus, striatum, cerebellum, mid‐brain, pons + medulla and cortex. The percentage increases after immobilization for 5 h were in the reverse order. The differences between the percentage decreases in the concentration of 5‐HIAA after hydrocortisone and the percentage increases after immobilization were very similar in all regions except the hypothalamus. This is consistent with immobilization stress increasing the firing rate of 5‐hydroxytryptaminergic neurones similarly in different regions. During the first 3 h of immobilization the concentrations of 5‐HIAA in the hypothalamus and in the rest of the brain increased approximately in parallel. Between 3 and 5 h, 5‐HIAA returned to control concentrations in the hypothalamus while continuing to rise in the rest of the brain. Relative changes in the concentration of 5‐HT in particulate and supernatant fractions after the various treatments were comparable except 2 h after kynurenine injection when the concentration of 5‐HT fell in the particulate but not in the supernatant fraction. The concentration of 5‐HT did fall in the latter, though more slowly than in the former fraction, suggesting a concentration of amine synthesizing organelles in particulate material. 1971 British Pharmacological Society