ENDOGENOUS SEROTONIN MODULATES HISTAMINE-RELEASE IN THE RAT HYPOTHALAMUS AS MEASURED BY IN-VIVO MICRODIALYSIS

In vivo microdialysis was used to study the effects of serotonergic dr ugs on histamine release from the suprachiasmatic nuclei region of the anterior hypothalamus in anesthetized rats. Local perfusion with sero tonin (5-hydroxytryptamine, 5-HT) increased histamine release signific antly and dose dependently. Methysergide (10 mg/kg i.p.), a 5-HT2C/(2A ) receptor antagonist, given 30 min before 5-HT perfusion, blocked the 5-HT-evoked histamine release. Methysergide (10 mg/kg i.p.), given al one, also suppressed basal histamine release by 33%. Dexfenfluramine ( 10 mu M), a 5-HT releaser and uptake blocker, administered via the mic rodialysis probe, significantly enhanced hypothalamic histamine releas e. With the same dose of dexfenfluramine, 5-HT release increased 10-fo ld in the same brain area. These results show for the first time that endogenous 5-HT modulates histamine release in vivo and it has a tonic stimulatory effect on the histaminergic nerve terminals of the rat an terior hypothalamus.