title: Evidence for the role of histamine H3 receptor in alcohol consumption and alcohol reward in mice.
abstract: Recent research suggests that histamine H3 receptor (H3R) antagonism may diminish motivational aspects of alcohol dependence. We studied the role of H3Rs in alcohol-related behaviors using H3R knockout (KO) mice and ligands. H3R KO mice consumed less alcohol than wild-type (WT) mice in a two-bottle free-choice test and in a 'drinking in the dark' model. H3R antagonist ciproxifan suppressed and H3R agonist immepip increased alcohol drinking in C57BL/6J mice. Impairment in reward mechanisms in H3R KO mice was confirmed by the lack of alcohol-evoked conditioned place preference. Plasma alcohol concentrations of H3R KO and WT mice were similar. There were no marked differences in brain biogenic amine levels in H3R KO mice compared with the control animals after alcohol drinking. In conclusion, the findings of this study provide evidence for the role of H3R receptor in alcohol-related behaviors, especially in alcohol drinking and alcohol reward. Thus, targeting H3Rs with a specific antagonist might be a potential means to treat alcoholism in the future.
authors.affiliation: Neuroscience Center and Institute of Biomedicine, Department of Anatomy, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
authors.forename: Saara
authors.initials: S
authors.lastname: Nuutinen
authors.forename: Minnamaija
authors.initials: M
authors.lastname: Lintunen
authors.forename: Jenni
authors.initials: J
authors.lastname: Vanhanen
authors.forename: Tiia
authors.initials: T
authors.lastname: Ojala
authors.forename: Stanislav
authors.initials: S
authors.lastname: Rozov
authors.forename: Pertti
authors.initials: P
authors.lastname: Panula
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D000818:Animals; D000431:Ethanol / Q000008:administration & dosage*; D018390:Gene Targeting; D017442:Histamine Agonists / Q000494:pharmacology; D054828:Histamine H3 Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011897:Random Allocation; D018100:Receptors, Histamine H3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012201:Reward
chemical_list: D017442:Histamine Agonists; D054828:Histamine H3 Antagonists; D018100:Receptors, Histamine H3; D000431:Ethanol