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 drugs on histamine release from the suprachiasmatic nuclei region of the anterior hypothalamus in anesthetized rats. Local perfusion with serotonin (5-hydroxytryptamine, 5-HT) increased histamine release significantly 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 alone, also suppressed basal histamine release by 33%. Dexfenfluramine (10 microM), a 5-HT releaser and uptake blocker, administered via the microdialysis probe, significantly enhanced hypothalamic histamine release. With the same dose of dexfenfluramine, 5-HT release increased 10-fold 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 anterior hypothalamus.