CENTRAL HISTAMINERGIC MECHANISMS MEDIATE THE VASOPRESSIN-INDUCED PITUITARY-ADRENOCORTICAL STIMULATION

Involvement of histamine receptors and hypothalamic and hippocampal hi stamine in stimulation of the hypothalamic-pituitary-adrenal (HPA) axi s by vasopressin (AVP) was investigated in conscious rats. The HPA act ivity was assessed by measuring serum corticosterone levels. One hour after administration AVP, (5 mu g/kg) given ip significantly raised th e serum corticosterone and hippocampal histamine levels, while the hyp othalamic histamine content was not affected. Pretreatment with the in hibitor of the brain histamine synthesis alpha-fluoromethylhistidine ( alpha-FMH) (50 mg/kg ip) considerably reduced both the AVP-elicited se rum corticosterone response and the hypothalamic and hippocampal hista mine levels. The histamine H-1- and H-2-receptor-antagonists mepyramin e (0.01 mg/kg) and ranitidine (0.1 mg/kg), given ip 15 min prior to AV P, significantly impaired the AVP-induced rise in the serum corticoste rone level and totally abolished the AVP-elicited increase in the hist amine content in the hippocampus; moreover mepyramine significantly lo wered this content in hypothalamus. Pretreatment with the histamine H- 3-receptor antagonist thioperamide (5 mg/kg ip) also significantly dec reased the AVP-elicited corticosterone response, but did not alter the histamine content in either brain structure examined. These results i ndicate that central histamine H-1-, H-2- and H-3-receptors significan tly mediate the stimulatory action of AVP on the pituitary-adrenocorti cal axis. Hippocampal histamine may be involved in mediation of the AV P-induced effect via H-1- and H-2-receptors. The inhibitory effect of thioperamide seems to be located directly at non H-3-intracellular sit es of the pituitary-adrenocortical axis.