The significance of brain histamine and its receptors in opioid stimulation of the pituitary-adrenocortical activity.

The involvement of brain histamine, contained in mast cells and neurons, and central histamine receptors in stimulation of the pituitary-adrenal axis by opioids was investigated indirectly through corticosterone secretion in conscious rats. The opioid agonists leu-enkephalinamide (DADL), morphine and b-endorphin (b-End) the s- m- and putative e-opioid receptor agonists, given intracerebroventricularly (ici) induced a significant, dose-dependent increase in serum corticosterone levels. The corticosterone response to b-End and morphine was significantly impaired by pretreatment with mepyramine and cimetidine, whereas the response to DADL was insensitive to histamine antagonists. Twenty four hours after administration of compound 48/80 the corticosterone responses to the opioids were greatly diminished. Pretreatment with a-fluoromethylhistidine (a-FMH), a histamine synthesis inhibitor, almost abolished the corticosterone response to DADL, b-End and morphine. These results indicate that central neuronal histamine and histamine receptors are significantly involved in the opioid-induced stimulation of the pituitary-adrenal axis in rats.