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Impaired cliff avoidance reaction in dopamine transporter knockout mice.
Psychopharmacology (Berl). 2013 Jun; 227(4):741-9.P

Abstract

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.

Authors+Show Affiliations

Department of Biological Psychiatry, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23397052

Citation

Yamashita, Motoyasu, et al. "Impaired Cliff Avoidance Reaction in Dopamine Transporter Knockout Mice." Psychopharmacology, vol. 227, no. 4, 2013, pp. 741-9.
Yamashita M, Sakakibara Y, Hall FS, et al. Impaired cliff avoidance reaction in dopamine transporter knockout mice. Psychopharmacology (Berl). 2013;227(4):741-9.
Yamashita, M., Sakakibara, Y., Hall, F. S., Numachi, Y., Yoshida, S., Kobayashi, H., Uchiumi, O., Uhl, G. R., Kasahara, Y., & Sora, I. (2013). Impaired cliff avoidance reaction in dopamine transporter knockout mice. Psychopharmacology, 227(4), 741-9. https://doi.org/10.1007/s00213-013-3009-9
Yamashita M, et al. Impaired Cliff Avoidance Reaction in Dopamine Transporter Knockout Mice. Psychopharmacology (Berl). 2013;227(4):741-9. PubMed PMID: 23397052.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2013/02/09/ PY - 2012/09/03/received PY - 2013/01/23/accepted PY - 2013/2/12/entrez PY - 2013/2/12/pubmed PY - 2013/12/19/medline SP - 741 EP - 9 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 227 IS - 4 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. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/23397052/Impaired_cliff_avoidance_reaction_in_dopamine_transporter_knockout_mice_ L2 - https://dx.doi.org/10.1007/s00213-013-3009-9 DB - PRIME DP - Unbound Medicine ER -