title: Impaired cliff avoidance reaction in dopamine transporter knockout mice.
abstract: BACKGROUND
  Impulsivity is a key feature of disorders that include attention-deficit/hyperactivity disorder (ADHD). The cliff avoidance reaction (CAR) assesses maladaptive impulsive rodent behavior. Dopamine transporter knockout (DAT-KO) mice display features of ADHD and are candidates in which to test other impulsive phenotypes.
  
  
  OBJECTIVE
  Impulsivity of DAT-KO mice was assessed in the CAR paradigm. For comparison, attentional deficits were also assessed in prepulse inhibition (PPI) in which DAT-KO mice have been shown to exhibit impaired sensorimotor gating.
  
  
  RESULTS
  DAT-KO mice exhibited a profound CAR impairment compared to wild-type (WT) mice. As expected, DAT-KO mice showed PPI deficits compared to WT mice. Furthermore, the DAT-KO mice with the most impaired CAR exhibited the most severe PPI deficits. Treatment with methylphenidate or nisoxetine ameliorated CAR impairments in DAT-KO mice.
  
  
  CONCLUSIONS
  These results suggest that DAT-KO mice exhibit impulsive CAR behavior that correlates with their PPI deficits. Blockade of monoamine transporters, especially the norepinephrine transporter (NET) in the prefrontal cortex (PFC), may contribute to pharmacological improvement of impulsivity in these mice.
authors: Department of Biological Psychiatry, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors: Motoyasu
authors: M
authors: Yamashita
authors: Yasufumi
authors: Y
authors: Sakakibara
authors: F Scott
authors: FS
authors: Hall
authors: Yohtaro
authors: Y
authors: Numachi
authors: Sumiko
authors: S
authors: Yoshida
authors: Hideaki
authors: H
authors: Kobayashi
authors: Osamu
authors: O
authors: Uchiumi
authors: George R
authors: GR
authors: Uhl
authors: Yoshiyuki
authors: Y
authors: Kasahara
authors: Ichiro
authors: I
authors: Sora
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000494:pharmacology; D007175:Impulsive Behavior / Q000503:physiopathology*; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D013216:Reflex, Startle / Q000187:drug effects; D055139:Sensory Gating / Q000187:drug effects / Q000502:physiology*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D005473:Fluoxetine; C011386:nisoxetine; D008774:Methylphenidate
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