Central H1- and H2-histaminergic stimulation of pituitary-adrenocortical response under stress in rats

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.