Interactions of histaminergic and serotonergic neurons in the hypothalamic regulation of prolactin and ACTH secretion

Serotonergic and histaminergic neuronal systems are both involved in mediation of the stress-induced release of the pituitary hormones prolactin (PRL) and ACTH. We investigated the possibility of an interaction between serotonin (5-HT) and histamine (HA) in regulation of PRL and ACTH secretion in conscious male rats. Animals were pretreated systemically with antagonists to 5-HT1, 5-HT2 or 5-HT3 receptors prior to intracerebroventricular (icv) administration of HA. The 5-HT1+2 receptor antagonist methysergide prevented and the 5-HT2 receptor antagonist LY 53857 attenuated the HA-induced PRL release while the 5-HT3 receptor antagonist ondansetron had no effect on this response. None of the three 5-HT receptor antagonists affected the ACTH response to HA. Specific blockade of HA synthesis by alpha-fluoromethylhistidine or blockade of postsynaptic HA receptors by icy infusion of the H-1 receptor antagonist mepyramine or the H-2 receptor antagonist cimetidine inhibited the PRL response to 5-HT or to the 5-HT precursor 5-hydroxytryptophan (5-HTP) given in combination with the 5-HT reuptake inhibitor fluoxetine (Fix). Blockade of the histaminergic system had no effect on the ACTH response to serotonergic stimulation. The H-3 receptors are inhibitory HA receptors. Systemic pretreatment with the H-3 receptor agonist R(alpha)methylhistamine, or the H-3 receptor antagonist thioperamide had no effect on the hormone response to activation of the serotonergic system by 5-HTP plus Flx, We conclude that the serotonergic and histaminergic neuronal systems interact in their stimulation of PRL secretion, but not in their stimulation of ACTH secretion. This interaction involves serotonergic 5-HT1 and 5-HT2 receptors and histaminergic H-1 and H-2 receptors. Furthermore, the previously observed inhibitory effect of the H-3 receptor agonist R(alpha)methylhistamine on stress-induced PRL and ACTH release seems not to be exerted by activation of presynaptic H-3 receptors located on serotonergic neurons but rather on histaminergic neurons.