Central H1- and H2-Histaminergic Stimulation of Pituitary-Adrenocortical Response under Stress in Rats

Abstract

In rats subjected to a mild stress of immobilization histamine, H₁-receptor agonist 2-pyridylethylamine (PEA), and H₂-receptor agonists, 4-methylhistamine (4-MHA) and dimaprit, given intraventricularly 60 min prior to stress, intensified the stress-induced increase of hypophyseal-adrenocortical response, evaluated indirectly through corticosterone concentration in blood serum. The effects were dose dependent and on a molar basis histamine and PEA were the most potent and 4-MHA and dimaprit were less effective, in this respect. The effect of histamine was almost totally blocked by both H₁-receptor antagonists, mepyramine or chloropyramine, and by H₂-receptor antagonists, metiamide or cimetidine. The corticosterone response to PEA was abolished by mepyramine, and the responses to 4-MHA or dimaprit were antagonized by cimetidine and metiamide. The response to the H₁ agonist was not substantially altered by pretreatment with cimetidine, and the responses to the H₂ agonists were not changed by mepyramine. These results suggest that in stressed rats the corticosterone response to histamine is mediated by both H₁ and H₂ central histamine receptors.