The influence of α-fluoromethylhistidine and histamine receptor antagonists on the β-endorphin-induced corticosterone response

Involvement of a central histaminergic mechanism in the stimulating effect of β-endorphin (β-End) on the pituitary-adrenocortical activity, measured indirectly through corticosterone secretion, was investigated in conscious rats. The rise in serum corticosterone levels, induced by β-End injected intraventricularly (icv) was considerably impaired by pretreatment with naltrexone, an opioid receptor antagonist. The stimulating effect of β-End was almost totally suppressed by a prior icv administration of mepyramine, a histamine H 1-receptor antagonist, and also considerably reduced by pretreatment with cimetidine, an H 2-receptor antagonist. The strongest suppression, by 83%; of the β-End-induced corticosterone response was evoked by a prior administration of α-fluoromethylhistidine, an inhibitor of neuronal histamine synthesis in the brain. These results indicate that both the brain neuronal histamine and central histamine H 1- and H 2-receptors are considerably involved in the β-endorphin-induced stimulation of the pituitary-adrenocortical activity.