The influence of alpha-fluoromethylhistidine and histamine receptor antagonists on the beta-endorphin-induced corticosterone response

Involvement of a central histaminergic mechanism in the stimulating effect of beta-endorphin (beta-End) on the pituitary-adrenocortical activity, measured indirectly through corticosterone secretion, was investigated in conscious rats. The rise in serum corticosterone levels, induced by beta-End injected intraventricularly (icv) was considerably impaired by pretreatment with naltrexone, an opioid receptor antagonist. The stimulating effect of beta-End was almost totally suppressed by a prior icv administration of mepyramine, a histamine H1-receptor antagonist, and also considerably reduced by pretreatment with cimetidine, an H2-receptor antagonist. The strongest suppression, by 83%; of the beta-End-induced corticosterone response was evoked by a prior administration of alpha-fluoromethylhistidine, an inhibitor of neuronal histamine synthesis in the brain. These results indicate that both the brain neuronal histamine and central histamine H1- and H2-receptors are considerably involved in the beta-endorphin-induced stimulation of the pituitary-adrenocortical activity.