title: Histamine H3 Receptor Regulates Sensorimotor Gating and Dopaminergic Signaling in the Striatum.
abstract: The brain histamine system has been implicated in regulation of sensorimotor gating deficits and in Gilles de la Tourette syndrome. Histamine also regulates alcohol reward and consumption via H3 receptor (H3R), possibly through an interaction with the brain dopaminergic system. Here, we identified the histaminergic mechanism of sensorimotor gating and the role of histamine H3R in the regulation of dopaminergic signaling. We found that H3R knockout mice displayed impaired prepulse inhibition (PPI), indicating deficiency in sensorimotor gating. Histamine H1 receptor knockout and histidine decarboxylase knockout mice had similar PPI as their controls. Dopaminergic drugs increased PPI of H3R knockout mice to the same level as in control mice, suggesting that changes in dopamine receptors might underlie deficient PPI response when H3R is lacking. Striatal dopamine D1 receptor mRNA level was lower, and D1 and D2 receptor-mediated activation of extracellular signal-regulated kinase 1/2 was absent in the striatum of H3R knockout mice, suggesting that H3R is essential for the dopamine receptor-mediated signaling. In conclusion, these findings demonstrate that H3R is an important regulator of sensorimotor gating, and the lack of H3R significantly modifies striatal dopaminergic signaling. These data support the usefulness of H3R ligands in neuropsychiatric disorders with preattentional deficits and disturbances in dopaminergic signaling.
authors.affiliation: Department of Anatomy, Faculty of Medicine and Neuroscience Center, University of Helsinki, Helsinki, Finland.
authors.forename: Jenni
authors.initials: J
authors.lastname: Kononoff Vanhanen
authors.affiliation: Department of Anatomy, Faculty of Medicine and Neuroscience Center, University of Helsinki, Helsinki, Finland.
authors.forename: Saara
authors.initials: S
authors.lastname: Nuutinen
authors.affiliation: Department of Anatomy, Faculty of Medicine and Neuroscience Center, University of Helsinki, Helsinki, Finland.
authors.forename: Mervi
authors.initials: M
authors.lastname: Tuominen
authors.affiliation: Department of Anatomy, Faculty of Medicine and Neuroscience Center, University of Helsinki, Helsinki, Finland pertti.panula@helsinki.fi.
authors.forename: Pertti
authors.initials: P
authors.lastname: Panula
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000502:physiology*; D006640:Histidine Decarboxylase / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D011969:Receptors, Histamine H1 / Q000235:genetics / Q000502:physiology; D018100:Receptors, Histamine H3 / Q000235:genetics / Q000502:physiology*; D013216:Reflex, Startle / Q000187:drug effects; D055139:Sensory Gating / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
chemical_list: D015259:Dopamine Agents; D011969:Receptors, Histamine H1; D018100:Receptors, Histamine H3; D006640:Histidine Decarboxylase