PMID- 29289701 OWN - NLM STAT- MEDLINE DCOM- 20200225 LR - 20230315 IS - 1873-5177 (Electronic) IS - 0091-3057 (Print) IS - 0091-3057 (Linking) VI - 178 DP - 2019 Mar TI - Dopamine transporter knockdown mice in the behavioral pattern monitor: A robust, reproducible model for mania-relevant behaviors. PG - 42-50 LID - S0091-3057(17)30545-2 [pii] LID - 10.1016/j.pbb.2017.12.007 [doi] AB - Efforts to replicate results from both basic and clinical models have highlighted problems with reproducibility in science. In psychiatry, reproducibility issues are compounded because the complex behavioral syndromes make many disorders challenging to model. We develop translatable tasks that quantitatively measure psychiatry-relevant behaviors across species. The behavioral pattern monitor (BPM) was designed to analyze exploratory behaviors, which are altered in patients with bipolar disorder (BD), especially during mania episodes. We have repeatedly assessed the behavioral effects of reduced dopamine transporter (DAT) expression in the BPM using a DAT knockdown (KD) mouse line (~10% normal expression). DAT KD mice exhibit a profile in the BPM consistent with acutely manic BD patients in the human version of the task-hyperactivity, increased exploratory behavior, and reduced spatial d (Perry et al., 2009). We collected data from multiple DAT KD BPM experiments in our laboratory to assess the reproducibility of behavioral outcomes across experiments. The four outcomes analyzed were: 1) transitions (amount of locomotor activity); 2) rearings (exploratory activity); 3) holepokes (exploratory activity); and 4) spatial d (geometrical pattern of locomotor activity). By comparing DAT KD mice to wildtype (WT) littermates in every experiment, we calculated effect sizes for each of the four outcomes and then calculated a mean effect size using a random effects model. DAT KD mice exhibited robust, reproducible changes in each of the four outcomes, including increased transitions, rearings, and holepokes, and reduced spatial d, vs. WT littermates. Our results demonstrate that the DAT KD mouse line in the BPM is a consistent, reproducible model of mania-relevant behaviors. More work must be done to assess reproducibility of behavioral outcomes across experiments in order to advance the field of psychiatry and develop more effective therapeutics for patients. CI - Copyright (c) 2017. Published by Elsevier Inc. FAU - Kwiatkowski, Molly A AU - Kwiatkowski MA AD - Department of Psychiatry, University of California San Diego, USA. FAU - Hellemann, Gerhard AU - Hellemann G AD - Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, USA. FAU - Sugar, Catherine A AU - Sugar CA AD - Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, USA.; Department of Biostatistics, University of California Los Angeles, USA. FAU - Cope, Zackary A AU - Cope ZA AD - Department of Psychiatry, University of California San Diego, USA. FAU - Minassian, Arpi AU - Minassian A AD - Department of Psychiatry, University of California San Diego, USA. FAU - Perry, William AU - Perry W AD - Department of Psychiatry, University of California San Diego, USA. FAU - Geyer, Mark A AU - Geyer MA AD - Department of Psychiatry, University of California San Diego, USA.; Research Service, VA San Diego Healthcare System, USA. FAU - Young, Jared W AU - Young JW AD - Department of Psychiatry, University of California San Diego, USA.; Research Service, VA San Diego Healthcare System, USA.. Electronic address: jaredyoung@ucsd.edu. LA - eng GR - R01 DA043535/DA/NIDA NIH HHS/United States GR - R01 MH104344/MH/NIMH NIH HHS/United States PT - Journal Article PT - Meta-Analysis DEP - 20171228 PL - United States TA - Pharmacol Biochem Behav JT - Pharmacology, biochemistry, and behavior JID - 0367050 RN - 0 (Antimanic Agents) RN - 0 (Dopamine Agonists) RN - 0 (Dopamine Plasma Membrane Transport Proteins) RN - 0 (Enzyme Inhibitors) RN - 0 (Quinolones) RN - 0 (Thiophenes) RN - 2J3YBM1K8C (brexpiprazole) RN - 614OI1Z5WI (Valproic Acid) RN - 658-48-0 (alpha-Methyltyrosine) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) SB - IM MH - Animals MH - Antimanic Agents/therapeutic use MH - Behavior, Animal/drug effects/*physiology MH - Bipolar Disorder/drug therapy/*physiopathology/psychology MH - Cohort Studies MH - *Disease Models, Animal MH - Dopamine Agonists/therapeutic use MH - Dopamine Plasma Membrane Transport Proteins/*genetics MH - Enzyme Inhibitors/pharmacology/therapeutic use MH - Exploratory Behavior/drug effects/physiology MH - *Gene Knockdown Techniques MH - Locomotion/drug effects/physiology MH - Mice MH - Mice, Inbred C57BL MH - Quinolones/therapeutic use MH - Reproducibility of Results MH - Thiophenes/therapeutic use MH - Tyrosine 3-Monooxygenase/antagonists & inhibitors MH - Valproic Acid/therapeutic use MH - alpha-Methyltyrosine/pharmacology/therapeutic use PMC - PMC10014035 MID - NIHMS1863121 OTO - NOTNLM OT - Bipolar disorder OT - Exploration OT - Hyperactivity OT - Meta-analysis OT - Reproducibility OT - Rodent COIS- Conflicts of Interest: none. EDAT- 2018/01/01 06:00 MHDA- 2020/02/26 06:00 PMCR- 2023/03/14 CRDT- 2018/01/01 06:00 PHST- 2017/09/11 00:00 [received] PHST- 2017/11/18 00:00 [revised] PHST- 2017/12/27 00:00 [accepted] PHST- 2018/01/01 06:00 [pubmed] PHST- 2020/02/26 06:00 [medline] PHST- 2018/01/01 06:00 [entrez] PHST- 2023/03/14 00:00 [pmc-release] AID - S0091-3057(17)30545-2 [pii] AID - 10.1016/j.pbb.2017.12.007 [doi] PST - ppublish SO - Pharmacol Biochem Behav. 2019 Mar;178:42-50. doi: 10.1016/j.pbb.2017.12.007. Epub 2017 Dec 28.