PMID- 25005251 OWN - NLM STAT- MEDLINE DCOM- 20150707 LR - 20211021 IS - 1740-634X (Electronic) IS - 0893-133X (Print) IS - 0893-133X (Linking) VI - 39 IP - 13 DP - 2014 Dec TI - Reduced dopamine transporter functioning induces high-reward risk-preference consistent with bipolar disorder. PG - 3112-22 LID - 10.1038/npp.2014.170 [doi] AB - Individuals with bipolar disorder (BD) exhibit deleterious decision making, negatively impacting their lives. Such aberrant decision making can be quantified using the Iowa Gambling Task (IGT), which requires choosing between advantageous and disadvantageous options based on different reward/punishment schedules. The mechanisms underlying this behavioral deficit are unknown, but may include the reduced dopamine transporter (DAT) functioning reported in BD patients. Using both human and mouse IGTs, we tested whether reduced DAT functioning would recreate patterns of deficient decision making of BD patients. We assessed the IGT performance of 16 BD subjects (7 female) and 17 healthy control (HC) subjects (12 female). We recorded standard IGT performance measures and novel post-reward and post-punishment decision-making strategies. We characterized a novel single-session mouse IGT using C57BL/6J mice (n = 44). The BD and HC IGT performances were compared with the effects of chronic (genetic knockdown (KD; n = 31) and wild-type (n = 28) mice) and acute (C57BL/6J mice (n = 89) treated with the DAT inhibitor GBR12909) reductions of DAT functioning in mice performing this novel IGT. BD patients exhibited impaired decision making compared with HC subjects. Both the good-performing DAT KD and GBR12909-treated mice exhibited poor decision making in the mouse IGT. The deficit of each population was driven by high-reward sensitivity. The single-session mouse IGT measures dynamic risk-based decision making similar to humans. Chronic and acute reductions of DAT functioning in mice impaired decision-making consistent with poor IGT performance of BD patients. Hyperdopaminergia caused by reduced DAT may impact poor decision making in BD patients, which should be confirmed in future studies. FAU - van Enkhuizen, Jordy AU - van Enkhuizen J AD - 1] Department of Psychiatry, University of California San Diego, La Jolla, CA, USA [2] Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. FAU - Henry, Brook L AU - Henry BL AD - Department of Psychiatry, University of California San Diego, La Jolla, CA, USA. FAU - Minassian, Arpi AU - Minassian A AD - Department of Psychiatry, University of California San Diego, La Jolla, CA, USA. FAU - Perry, William AU - Perry W AD - Department of Psychiatry, University of California San Diego, La Jolla, CA, USA. FAU - Milienne-Petiot, Morgane AU - Milienne-Petiot M AD - 1] Department of Psychiatry, University of California San Diego, La Jolla, CA, USA [2] Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. FAU - Higa, Kerin K AU - Higa KK AD - Department of Psychiatry, University of California San Diego, La Jolla, CA, USA. FAU - Geyer, Mark A AU - Geyer MA AD - 1] Department of Psychiatry, University of California San Diego, La Jolla, CA, USA [2] Research Service, VA San Diego Healthcare System, San Diego, CA, USA. FAU - Young, Jared W AU - Young JW AD - 1] Department of Psychiatry, University of California San Diego, La Jolla, CA, USA [2] Research Service, VA San Diego Healthcare System, San Diego, CA, USA. LA - eng GR - R01-MH042228/MH/NIMH NIH HHS/United States GR - R01 MH104344/MH/NIMH NIH HHS/United States GR - R01-MH071916/MH/NIMH NIH HHS/United States GR - R01 MH071916/MH/NIMH NIH HHS/United States GR - R25 MH081482/MH/NIMH NIH HHS/United States GR - R01 MH042228/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20140709 PL - England TA - Neuropsychopharmacology JT - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JID - 8904907 RN - 0 (Dopamine Plasma Membrane Transport Proteins) RN - 0 (Dopamine Uptake Inhibitors) RN - 0 (Piperazines) RN - 90X28IKH43 (vanoxerine) SB - IM MH - Adolescent MH - Adult MH - Animals MH - Bipolar Disorder/*psychology MH - Conditioning, Operant/drug effects MH - Decision Making/drug effects/*physiology MH - Dopamine Plasma Membrane Transport Proteins/*deficiency/genetics MH - Dopamine Uptake Inhibitors/pharmacology MH - Female MH - Games, Experimental MH - Gene Expression Regulation/drug effects MH - Humans MH - Impulsive Behavior/drug effects/physiology MH - Individuality MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Middle Aged MH - Piperazines/pharmacology MH - *Reward MH - *Risk-Taking MH - Young Adult PMC - PMC4229584 EDAT- 2014/07/10 06:00 MHDA- 2015/07/08 06:00 PMCR- 2015/12/01 CRDT- 2014/07/10 06:00 PHST- 2014/03/06 00:00 [received] PHST- 2014/06/25 00:00 [revised] PHST- 2014/06/28 00:00 [accepted] PHST- 2014/07/10 06:00 [entrez] PHST- 2014/07/10 06:00 [pubmed] PHST- 2015/07/08 06:00 [medline] PHST- 2015/12/01 00:00 [pmc-release] AID - npp2014170 [pii] AID - 10.1038/npp.2014.170 [doi] PST - ppublish SO - Neuropsychopharmacology. 2014 Dec;39(13):3112-22. doi: 10.1038/npp.2014.170. Epub 2014 Jul 9.