In vivo modulation of rat hypothalamic histamine release by the histamine H-3 receptor ligands, immepip and clobenpropit. Effects of intrahypothalamic and peripheral application

We investigated the effect of the new potent and selective histamine H-3 re ceptor agonist, immepip, and the histamine H-3 receptor antagonist, clobenp ropit, on in vivo neuronal histamine release from the anterior hypothalamic area of urethane-anesthetized rats, using microdialysis. Intrahypothalamic perfusion with immepip af:concentrations of 1 and 10 nM reduced histamine release to 75% and 35% of its basal level, respectively. Peripheral injecti on of immepip (5 mg/kg) caused a sustained decrease in histamine release of 50%. Clobenpropit potently increased histamine release after intrahypothal amic perfusion. The maximal increase in histamine release was 2-fold, obser ved at a concentration of 10 nM clobenpropit. Peripheral injection of clobe npropit (5-15 mg/kg) increased histamine release to about 150% of the basal value. A more marked increase in histamine release was found after injecti on of the histamine H-3 receptor antagonist, thioperamide (5 mg/kg). In con clusion, intrahypothalamic perfusion of the histamine H3 receptor agonist, immepip and the histamine H-3 receptor antagonist, clobenpropit, potently a nd oppositely modulated in vivo histamine release from the anterior hypotha lamic area. The decreased histamine release after peripheral injection of i mmepip indicates that this novel agonist readily crosses the blood-brain ba rrier, making it a potential candidate for in vivo histamine H-3 receptor s tudies. The differential increase in histamine release after peripheral inj ection of clobenpropit and thioperamide is discussed. (C) 1998 Elsevier Sci ence B.V. All rights reserved.