Adrenocorticoids control 5-hydroxytryptamine metabolism in rat brain.

The influence of surgical adrenalectomy was examined on the biosynthetic capacity for 5-hydroxytryptamine of rat brain. The results demonstrate that adrenalectomy decreased tryptophan hydroxylase activity and its substrate tryptophan in the brain stem. A parallel change in the concentration of 5-hydroxytryptamine was seen in brain stem and striatal region of adrenalectomized rats. In contrast, the level of 5-hydroxyindoleacetic acid was significantly elevated in both of these brain regions. Replacement therapy with corticosterone (10 mg/kg i.p.) produced time-dependent increases in tryptophan, tryptophan hydroxylase and 5-hydroxytryptamine and decreases in 5-hydroxyindoleacetic acid levels. Alterations in these neurochemical parameters were more conspicuous in adrenalectomized rats receiving corticosterone for 7 days as compared to those given only for 3 days. Our data demonstrate that adrenocortical hormones regulate brain 5-hydroxytryptamine synthesis probably by enhancing both the levels of tryptophan and the activity of rate-limiting enzyme tryptophan hydroxylase. It is postulated that emotional instability seen during altered adrenocortical function might partly be associated with abnormal metabolism of central 5-hydroxytryptamine.