A Role for Serotonin in the Hypothalamic-Pituitary-Adrenal Response to Insulin Stress

Abstract

Controversy exists concerning the possible involvement of serotonin (5-HT) in the pituitary-adrenocortical response to stress. In the present research, a variety of pharmacological and physiological manipulations were used in male rats to study the role of this neurotransmitter in the adrenocortical response to insulin-induced hypoglycemia. We first examined the effect of insulin stress on hypothalamic 5-HT metabolism and found increased turnover as determined by an enhanced accumulation of 5-HT following monoamine oxidase inhibition. Brain 5-HT depletion by intraventricular injection of 5,7-dihydroxytryptamine significantly attenuated the corticosterone response to insulin, while treatment with the 5-HT receptor blocker methysergide tended to have the same effects. The corticosterone response to insulin was potentiated by prior administration of L-tryptophan, and blocked by pretreatment with valine, an amino acid that competes with tryptophan for transport across the blood-brain barrier. It therefore appears that the pituitary-adrenal response to insulin is mediated at least in part by 5-HT, and may be dependent on increased uptake of tryptophan by the brain.

Central serotonergic stimulation of aldosterone secretion.

“…Serotonin has also been found to be involved in the stimulation of the hypothalamic-pituitaryadrenal axis induced by insulin hypoglycemia (48). It has been postulated that serotonin plays a role in the regulation of ACTH secretion by pituitary intermediate lobe adenomas, causing Cushing's syndrome (49).…”

ACTH/Cortisol Involvement in the Serotonergic Disorder Affecting the Parkinsonian Brain

“…see ref . 18] and that it is involved not only in the control of the ACTH/corticosterone response to stress or to insulin administration [19,20], but also in regulation of the ACTH/corticosterone rise during the morning hours [21,22], Corticosteroids and ACTH have a diurnal rhythm with a nadir in the light period and peak secretion during the dark period [23]. Studies of Bellomo et al [24] have shown lower 24-hour integrated concentra tions of ACTH/cortisol in parkinsonian patients as com pared with normal controls and have suggested that a hypothalamic disturbance is responsible for this disorder.…”

“…This alteration may also be produced by deficient serotonergic control of ACTH. Studies in rats have shown that acute stress alters the serotonergic activity in the brain in normal conditions [28], Furthermore, insulin-induced hypoglycemia in creases 5-HT turnover in the rat hypothalamus [20], and acute immobilization of rats for 1-3 h elevates both plas ma corticosterone and 5-HT levels in several brain parts. The majority of the results with 5-HT agonists and antag onists argue in favor of a stimulatory action of 5-HT on stress-induced ACTH/corticosteroid secretion.…”

Self-biting with multiple finger amputations following spinal cord injury

“…Since stress and SCI have also been associated with such imbalances, they may contribute to SIB through that mechanism. SER activity increases (Culman, 1984;Driscoll, 1983;Richardson, 1984;Yehuda, 1984) or decreases (Driscoll, 1983;Smythe, 1983) in areas of the brain after stress. In humans, central SER stores are depleted (Hoes, 1982).…”