Effects of histamine H-3 receptor ligands in experimental models of anxiety and depression

Histamine H-3 receptor ligands have been proposed to be of potential therap eutic interest for the treatment of different central nervous system disord ers; however, the psychopharmacological properties of these drugs have not been studied extensively. In this work, we investigated the possible involv ement of histamine H-3 receptor function in experimental models of anxiety (elevated plus-maze) and depression (forced swimming test). Male Sprague-Da wley rats were treated IP with the histamine H-3 receptor agonist R-alpha-m ethylhistamine (10 mg/kg) or the histamine H-3 receptor antagonist thiopera mide (0.2, 2 and 10 mg/kg) and 30 min afterwards the time spent in the open arms of an elevated plus-maze was registered for 5 min. The immobility tim e of male OF1 mice in the forced swimming test was recorded for 6 min, 1 h after the IP administration of R-alpha-methylhistamine (10 and 20 mg/kg), t hioperamide (0.2, 2, 10 and 20 mg/kg) or another histamine H-3 receptor ant agonist? clobenpropit (5 mg/kg). The locomotor activity of mice was checked in parallel by means of an activity meter. Both saline controls and active drug controls were used in all the paradigms. Neither thioperamide nor R-a lpha-methylhistamine significantly changed animal behaviour in the elevated plus-maze. R-alpha-methylhistamine and the higher dose of thioperamide ass ayed (20 mg/kg) were also inactive in the forced swimming test. By contrast , thioperamide (0.2-10 mg/kg) dose-dependently decreased immobility, the ef fect being significant at 10 mg/kg (33% reduction of immobility); clobenpro pit produced an effect qualitatively similar (24% reduction of immobility). None of these histamine H-3 receptor antagonists affected locomotor activi ty. These preliminary results suggest that the histamine H-3 receptor block ade could be devoid of anxiolytic potential but have antidepressant effects . Besides, the stimulation of these receptors does not seem to be followed by changes in the behavioural parameters studied.