title: Possible role of the dopamine D1 receptor in the sensorimotor gating deficits induced by high-fat diet.
abstract: BACKGROUND
  High-fat diet (HFD) has been recently reported to induce sensorimotor gating deficits, but the underlying mechanisms are not well understood.
  
  
  OBJECTIVE
  The purpose of this study is to determine whether HFD induces long-lasting deficits in sensorimotor gating and to examine the involvement of altered dopamine (DA) function.
  
  
  METHODS
  C57BL/6J mice were fed HFD for 10 weeks and then normal diet (ND) for 4 weeks. DA D2 receptor (D2R) knockout (KO) mice were also fed HFD for 10 weeks. The mice were evaluated for prepulse inhibition (PPI) of acoustic startle after HFD and the subsequent 4-week ND. We evaluated the effect of SCH23390, a D1 receptor (D1R) antagonist, on PPI and measured protein expression levels of D1R and D2R in the prefrontal cortex (PFC) in HFD mice. The concentrations of monoamines and their metabolites in the cortices of 10-week HFD or ND mice were measured using high performance liquid chromatography.
  
  
  RESULTS
  Long-term HFD-induced PPI disruption in WT and D2R KO mice. Even after 4 weeks of subsequent ND, PPI remained to be disrupted. SCH23390 mitigated the PPI disruption. In HFD animals, D1R protein expression in the PFC was significantly decreased, while DA, homovanillic acid, and 3,4-dihydroxyphenylacetic acid levels in the cortex were increased.
  
  
  CONCLUSIONS
  This is the first evidence that HFD can induce long-lasting deficits in sensorimotor gating through alteration of cortical levels of DA and its metabolites. Our data suggest that HFD-induced PPI deficits are related to altered D1R signaling and that D1R antagonists may have therapeutic effects on the deficits.
authors.affiliation: Department of Mental Disorder Research, National Center of Neurology and Psychiatry, National Institute of Neuroscience, 4-1-1, Ogawa-higashi, Kodaira, Tokyo, 187-8502, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Wakabayashi
authors.affiliation: Department of Mental Disorder Research, National Center of Neurology and Psychiatry, National Institute of Neuroscience, 4-1-1, Ogawa-higashi, Kodaira, Tokyo, 187-8502, Japan.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Numakawa
authors.affiliation: Department of Mental Disorder Research, National Center of Neurology and Psychiatry, National Institute of Neuroscience, 4-1-1, Ogawa-higashi, Kodaira, Tokyo, 187-8502, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Ooshima
authors.affiliation: Department of Mental Disorder Research, National Center of Neurology and Psychiatry, National Institute of Neuroscience, 4-1-1, Ogawa-higashi, Kodaira, Tokyo, 187-8502, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Hattori
authors.affiliation: Department of Mental Disorder Research, National Center of Neurology and Psychiatry, National Institute of Neuroscience, 4-1-1, Ogawa-higashi, Kodaira, Tokyo, 187-8502, Japan. hkunugi@ncnp.go.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D059305:Diet, High-Fat; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D065808:Prepulse Inhibition / Q000187:drug effects / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology; D055139:Sensory Gating / Q000187:drug effects* / Q000502:physiology
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C534628:SCH 23390; D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine; D006719:Homovanillic Acid
keywords: Cortex; Dopamine D1 receptor; Dopamine D2 receptor; High-fat diet; Monoamine; Prepulse inhibition