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

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.