TY - JOUR
T1 - Impaired cliff avoidance reaction in dopamine transporter knockout mice
AU - Yamashita, Motoyasu
AU - Sakakibara, Yasufumi
AU - Hall, F. Scott
AU - Numachi, Yohtaro
AU - Yoshida, Sumiko
AU - Kobayashi, Hideaki
AU - Uchiumi, Osamu
AU - Uhl, George R.
AU - Kasahara, Yoshiyuki
AU - Sora, Ichiro
N1 - Funding Information:
Acknowledgments This study was supported by a Grant-in-Aid for Health and Labour Science Research (Research on Pharmaceutical and Medical Safety) from MHLW of Japan; by Grants-in-Aid for Core Research for Evolutional Science and Technology (CREST), Global COE Program (Basic & Translational Research Center for Global Brain Science) from MEXT of Japan and through funding from the Intramural Research Program of the National Institute on Drug Abuse, NIH/DHHS, USA (GRU and FSH). All animal experiments were performed in accordance with the guidelines of the Animal Ethics Committee at Tohoku University Graduate School of Medicine (Sen-dai, Japan). No authors have any other conflicts of interest or financial disclosures to make.
PY - 2013/6
Y1 - 2013/6
N2 - Rationale: 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. Objectives: 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. Conclusion: 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.
AB - Rationale: 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. Objectives: 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. Conclusion: 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.
KW - Attention-deficit/hyperactivity disorder
KW - Behavioral inhibition
KW - Cliff avoidance reaction
KW - Dopamine transporter knockout mice
KW - Impulsivity
KW - Prepulse inhibition of acoustic startle response
UR - http://www.scopus.com/inward/record.url?scp=84878704262&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878704262&partnerID=8YFLogxK
U2 - 10.1007/s00213-013-3009-9
DO - 10.1007/s00213-013-3009-9
M3 - Article
C2 - 23397052
AN - SCOPUS:84878704262
VL - 227
SP - 741
EP - 749
JO - Psychopharmacology
JF - Psychopharmacology
SN - 0033-3158
IS - 4
ER -