ANTIDEPRESSANT-LIKE EFFECTS OF ENDOGENOUS HISTAMINE AND OF 2 HISTAMINE H-1 RECEPTOR AGONISTS IN THE MOUSE FORCED SWIM TEST

1 Effects of substances which are able to alter brain histamine levels and two histamine H-1 receptor agonists were investigated in mice by means of an animal model of depression, the forced swim test. 2 Imipra mine (10 and 30 mg kg(-1), i.p.) and amitriptyline (5 and 15 mg kg(-1) , i.p.) were used as positive controls. Their effects were not affecte d by pretreatment with the histamine H-3 receptor agonist, (R)-alpha-m ethylhistamine, at a dose (10 mg kg(-1), i.p.) which did not modify th e cumulative time of immobility. 3 The histamine H-3 receptor antagoni st, thioperamide (2-20 mg kg(-1), s.c.), showed an antidepressant-like effect, with a maximum at the dose of 5 mg kg(-1), which was complete ly prevented by (R)-alpha-methylhistamine. 4 The histamine-N-methyltra nsferase inhibitor, metoprine (2-20 mg kg(-1), s.c.), was effective wi th an ED50 Of 4.02 (2.71-5.96) mg kg(-1); its effect was prevented by (R) -alpha-methylhistamine. 5 The histamine precursor, L-histidine (10 0-1000 mg kg(-1), i.p.), dose-dependently decreased the time of immobi lity [ED30 587 (499-712) mg kg(-1)]. The effect of 500 mg kg(-1) L-his tidine was completely prevented by the selective histidine decarboxyla se inhibitor, (S)-alpha-fluoromethylhistidine (50 mg kg(-1), i.p.), ad ministered 15 h before. 6 The highly selective histamine H-1 receptor agonist, 2-(3-trifluoromethylphenyl)histamine (0.3-6.5 mu g per mouse, i.c.v.), and the better known H-1 agonist, 2-thiazolylethylamine (0.1 -1 mu g per mouse, i.c.v.), were both dose-dependently effective in de creasing the time of immobility [ED50 3.6 (1.53-8.48) and 1.34 (0.084- 21.5) mu g per mouse, respectively]. 7 None of the substances tested a ffected mouse performance in the rota rod test at the doses used in th e forced swim test. 8 It was concluded that endogenous histamine reduc es the time of immobility in this test, suggesting an antidepressant-l ike effect, via activation of H-1 receptors.