INFLUENCE OF THE CENTRAL HISTAMINERGIC SYSTEMS ON THE PITUITARY-ADRENOCORTICAL RESPONSE TO MET-ENKEPHALINAMIDE

A possible involvement of hypothalamic histamine and histamine recepto rs in the hypothalamic-pituitary-adrenocortical (HPA) activity stimula ted by Met-enkephalinamide (DADM) was investigated indirectly by corti costerone secretion in conscious rats. DADM, a delta-opioid receptor a gonist, given intracerebroventricularly (ivc) induced a significant in crease in the serum corticosterone level, which was considerably reduc ed by ip or icv pretreatment with naltrexone, an opioid antagonist. Pr etreatment with alpha-fluoromethylhistidine (alpha-FMH) 20 mg/kg ip or 50 mu g icy, an inhibitor of the brain histamine synthesis, drastical ly 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 H-1- and H-2-receptor antagonists, did not substantially change the corticoste rone response to DADM. The present results suggest that DADM stimulate s the HPA activity via central delta-opioid receptors. They also indic ate that the reduction of the HPA response to DADM by alpha-FMH is con nected with significant diminution of hypothalamic histamine, but not noradrenaline or dopamine levels. Central histamine receptors do not m ediate the metenkephalinamide-induced HPA stimulation.