STIMULATION OF THE HYPOTHALAMO-PITUITARY-ADRENOCORTICAL AXIS BY THE CENTRAL SEROTONERGIC PATHWAY - INVOLVEMENT OF ENDOGENOUS CORTICOTROPIN-RELEASING HORMONE BUT NOT VASOPRESSIN

Many reports indicate that serotonin plays a role in the regulation of the hypothalamo-pituitary-adrenocortical axis. The present study was designed to elucidate whether the activation of the central serotonergic pathway enhances adrenocorticotropin and corticosterone secretion, and if so, whether the CRH and vasopressin neuronal systems could be mediating this effect. Intraperitoneal administration of a low dose of L-5-hydroxytryptophan (an aromatic L-amino acid precursor of serotonin synthesis; 20 mg/kg bw, 30 minutes before the sacrifice) in rats pretreated with pargyline (a brain mononoamine oxidase inhibitor, which enhances monoamine activity; 75 mg/Kg bw, 16 hours before the sacrifice) and carbidopa (a peripheral active inhibitor of the decarboxylation of aromatic L-amino acids, which would permit more monoamine precursor to be available to the brain; 50 mg/Kg bw, 90 minutes before the sacrifice) increased ACTH and corticosterone secretion in plasma. Such an effect was partially blocked by metergoline (a serotonin type-1 and -2 receptor blocker; 1 mg/Kg bw, 90 minutes before the sacrifice), but not by spiperone (a serotonin type-2 and dopamine receptor antagonist; 0.5 mg/Kg bw, 90 minutes before the sacrifice). The activation of the central serotonergic system enhanced the CRH content in the median eminence, whereas it decreased the content of this neuropeptide in the medial basal hypothalamus. These effects were fully abolished by metergoline, but not by spiperone pretreatment. The activation of the serotonergic pathway did not influence the vasopressinergic neuronal system. In vitro experiments using hypothalamic-median eminence fragments incubated with serotonin solutions indicate that this monoamine possesses a CRH releasing effect at concentrations of 1-mu-M or more. The CRH secretagogue activity of serotonin (1-mu-M) was completely blocked by metergoline (1-mu-M) but not by spiperone (1-mu-M). Conversely, serotonin did not induce a significant release of vasopressin at any of the concentrations assayed. These studies strongly suggest that the enhanced pituitary-adrenocortical function after the activation of the central serotonergic pathway could be due, at least in part, through the stimulation of the CRH but not the vasopressinergic neuronal system.