Influence of the central histaminergic systems on the pituitary-adrenocortical response to met-enkephalinamide

A possible involvement of hypothalamic histamine and histamine receptors in the hypothalamic-pituitary-adrenocortical (HPA) activity stimulated by Met-enkephalinamide (DADM) was investigated indirectly by corticosterone secretion in conscious rats. DADM, a delta-opioid receptor agonist, given intracerebroventricularly (i.v.c.) induced a significant increase in the serum corticosterone level, which was considerably reduced by ip or icv pretreatment with naltrexone, an opioid antagonist. Pretreatment with alpha-fluoromethylhistidine (alpha-FMH) 20 mg/kg ip or 50 micrograms icv, an inhibitor of the brain histamine synthesis, drastically reduced the hypothalamic histamine level, did not affect the levels of noradrenaline and dopamine, and almost abolished the DADM-induced corticosterone response. Mepyramine and cimetidine, histamine H1- and H2-receptor antagonists, did not substantially change the corticosterone response to DADM. The present results suggest that DADM stimulates the HPA activity via central delta-opioid receptors. They also indicate that the reduction of the HPA response to DADM by alpha-FMH is connected with significant diminution of hypothalamic histamine, but not noradrenaline or dopamine levels. Central histamine receptors do not mediate the metenkephalinamide-induced HPA stimulation.