title: Mouse light/dark box test reveals anxiogenic-like effects by activation of histamine H1 receptors.
abstract: Effects of substances that are able to alter the histamine level, a histamine H(1)-receptor agonist and antagonist, and a histamine H(2)-receptor agonist were investigated in an anxiety-like state in mice by means of the light/dark box test. Diazepam was used as positive control. The histamine H(3)-receptor antagonist, thioperamide (2, 5, and 20 mg/kg s.c.), showed an anxiogenic-like effect that reached a maximum with the dosage of 5 mg/kg. The histamine-N-methyltransferase (HMT) inhibitor, metoprine (5 and 20 mg/kg s.c.), also decreased the time in the light at the highest dose used and, likewise, the highly selective histamine H(1)-receptor agonist, 2-(3-trifluoromethylphenyl)histamine (FMPH) (2.65 and 6.5 microg/mouse, i.c.v.). On the contrary, the histamine H(2)-receptor agonist, impromidine (3, 10, 20, and 30 microg/mouse, i.c.v.), dose-dependently showed an anxiolytic-like effect. The selective histamine H(1) antagonist, pyrilamine (20 mg/kg i.p.) was able to prevent the anxiogenic-like effect of FMPH significantly, and that of thioperamide partially, while the effect caused by metoprine remained unvaried. It is suggested that the histaminergic system modulates anxiety-like states via the activation of both postsynaptic receptors in a contrasting manner: activation of the H(1) receptor causes an anxiogenic-like effect, while that of the H(2) receptors reduces anxiousness. However, on the basis of effects observed with the substances capable of releasing endogenous histamine, it seems likely that the anxiogenic-like effect is prevalent.
authors.affiliation: Department of Preclinical and Clinical Pharmacology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy. malmberg@server1.pharm.unifi.it
authors.forename: Petra
authors.initials: P
authors.lastname: Malmberg-Aiello
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ipponi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bartolini
authors.forename: Walter
authors.initials: W
authors.lastname: Schunack
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000378:metabolism*; D003624:Darkness; D017442:Histamine Agonists / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects / Q000502:physiology; D008027:Light; D008297:Male; D051379:Mice; D010880:Piperidines / Q000494:pharmacology; D011739:Pyrimethamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000378:metabolism* / Q000502:physiology
chemical_list: D017442:Histamine Agonists; D006634:Histamine H1 Antagonists; D010880:Piperidines; D011969:Receptors, Histamine H1; C006308:metoprine; C052075:thioperamide; D011739:Pyrimethamine