title: Modulation of behavior by the histaminergic system: lessons from H(1)R-and H(2)R-deficient mice.
abstract: Besides acting in the immune system, histamine is also a neurotransmitter in the central nervous system. The H1R causes central side effects, e.g. of first generation antihistamines, antidepressants or antipsychotics and represents the component of the central histaminergic system most extensively studied in behavior experiments with knock-out mice. Central effects of H2R are similar, but only few behavioral results from knockout models are available. We summarize the behavior phenotype of H1R- and H2R-deficient mice, revealing histaminergic modulation of behaviors like locomotor activity, cognition, emotional states, arousal, sleep and wakefulness, circadian rhythm, pain perception, food intake and energy consumption, respiration and susceptibility to seizures. Knock-out models demonstrate several central effects of H1R and H2R that are not clinically and therapeutically exploited to date. We critically discuss problems and pitfalls of both the knock-out mouse technique and the pharmacological approach with receptor-selective ligands. The behavioral characterization of Hrh1(-/-)- and Hrh2(-/-)-mice is crucial, because many pharmacological agents lack the required selectivity to unequivocally address the functions of a single histamine receptor subtype.
authors.affiliation: Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. Electronic address: schneider.erich@mh-hannover.de.
authors.forename: Erich H
authors.initials: EH
authors.lastname: Schneider
authors.affiliation: Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Neumann
authors.affiliation: Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Seifert
mesh_terms: D000818:Animals; D001519:Behavior / Q000502:physiology*; D001921:Brain / Q000502:physiology; D006801:Humans; D018345:Mice, Knockout; D011969:Receptors, Histamine H1 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D011970:Receptors, Histamine H2 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2
keywords: Behavior; Brain; Circadian rhythm; Food intake; Histamine receptor; Knockout mouse; Learning; Memory; Pain; Respiration; Seizures; Sleep