Evidence for the role of histamine H3 receptor in alcohol consumption and alcohol reward in mice

Saara Nuutinen (1) , Minnamaija Lintunen (1) , Jenni Vanhanen (1) , Tiia Ojala (1) , Stanislav Rozov (1) , Pertti Panula (1)

1 Neuroscience Center and Institute of Biomedicine, Anatomy

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 wildtype (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 to the control animals after alcohol drinking. In conclusion, the findings of the present study provide evidence for the role of H3R receptor in alcohol-related behaviours, 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.

Mots clés: Alcohol & Alcoholism; Addiction & Substance Abuse; Dopamine; Animal models; histamine; two-bottle choice test; drinking in the dark

Saara Nuutinen, Minnamaija Lintunen, Jenni Vanhanen, Tiia Ojala, Stanislav Rozov, et al.. Evidence for the role of histamine H3 receptor in alcohol consumption and alcohol reward in mice. Neuropsychopharmacology, 2011, ⟨10.1038/npp.2011.90⟩. ⟨hal-00649453⟩