title: Enhanced prepulse inhibition and low sensitivity to a dopamine agonist in HESR1 knockout mice.
abstract: Transcription factor Hesr family genes are important in neuronal development. We demonstrated previously that HESR1 and HESR2 modified expression of the dopamine transporter (DAT) reporter gene. HESR-family genes have been investigated in development, but their functions, especially in relation to behaviors regulated by dopamine, in adult animals remain unclear. In the present study, we investigated the effects of Hesr1 and Hesr2 on behavior. A behavioral test battery to examine spontaneous activity, anxiety-like behavior, aggressive behavior, pain sensitivity, and sensorimotor gating was conducted in Hesr1 and Hesr2 knockout (KO) mice. Enhanced prepulse inhibition (PPI), which is a form of sensorimotor gating, was observed in only Hesr1 KO mice; other behavioral traits were mostly comparable to wild-type animals in both the Hesr1 and the Hesr2 KO lines. Next, we used a dopamine agonist, apomorphine, to confirm the involvement of the dopaminergic system. Injection of apomorphine reduced the enhanced PPI in Hesr1 KO mice. Additionally, dose-dependent sensitivity to the agonist was lower in the Hesr1 KO mice than in wild-type mice, suggesting that the enhanced PPI resulted from this alteration in dopamine sensitivity. Furthermore, DAT mRNA was downregulated in Hesr1 KO mice, whereas the dopamine D1 and D2 receptors were comparable. These findings suggest Hesr1 to be a novel factor that affects dopamine sensitivity and the sensorimotor gating system.
authors.affiliation: Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Kouta
authors.initials: K
authors.lastname: Kanno
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kokubo
authors.forename: Aki
authors.initials: A
authors.lastname: Takahashi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Koide
authors.forename: Shoichi
authors.initials: S
authors.lastname: Ishiura
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics; D018797:Cell Cycle Proteins / Q000172:deficiency* / Q000235:genetics; D003623:Dark Adaptation / Q000187:drug effects / Q000235:genetics; D018491:Dopamine Agonists / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D013216:Reflex, Startle / Q000187:drug effects*; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics; D055139:Sensory Gating / Q000187:drug effects*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: D001058:Apomorphine; D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D018491:Dopamine Agonists; D012097:Repressor Proteins; D014446:Tyrosine 3-Monooxygenase; C120420:Hey1 protein, mouse; C485778:Hey2 protein, mouse
keywords: Hesr1; Hesr2; apomorphine; dopamine receptor; dopamine transporter