Dopamine transporter knockdown mice in the behavioral pattern monitor: A robust, reproducible model for mania-relevant behaviors.
Animals
Antimanic Agents
/ therapeutic use
Behavior, Animal
/ drug effects
Bipolar Disorder
/ drug therapy
Cohort Studies
Disease Models, Animal
Dopamine Agonists
/ therapeutic use
Dopamine Plasma Membrane Transport Proteins
/ genetics
Enzyme Inhibitors
/ pharmacology
Exploratory Behavior
/ drug effects
Gene Knockdown Techniques
Locomotion
/ drug effects
Mice
Mice, Inbred C57BL
Quinolones
/ therapeutic use
Reproducibility of Results
Thiophenes
/ therapeutic use
Tyrosine 3-Monooxygenase
/ antagonists & inhibitors
Valproic Acid
/ therapeutic use
alpha-Methyltyrosine
/ pharmacology
Bipolar disorder
Exploration
Hyperactivity
Meta-analysis
Reproducibility
Rodent
Journal
Pharmacology, biochemistry, and behavior
ISSN: 1873-5177
Titre abrégé: Pharmacol Biochem Behav
Pays: United States
ID NLM: 0367050
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
11
09
2017
revised:
18
11
2017
accepted:
27
12
2017
pubmed:
1
1
2018
medline:
26
2
2020
entrez:
1
1
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 29289701
pii: S0091-3057(17)30545-2
doi: 10.1016/j.pbb.2017.12.007
pmc: PMC10014035
mid: NIHMS1863121
pii:
doi:
Substances chimiques
Antimanic Agents
0
Dopamine Agonists
0
Dopamine Plasma Membrane Transport Proteins
0
Enzyme Inhibitors
0
Quinolones
0
Thiophenes
0
brexpiprazole
2J3YBM1K8C
Valproic Acid
614OI1Z5WI
alpha-Methyltyrosine
658-48-0
Tyrosine 3-Monooxygenase
EC 1.14.16.2
Types de publication
Journal Article
Meta-Analysis
Langues
eng
Sous-ensembles de citation
IM
Pagination
42-50Subventions
Organisme : NIDA NIH HHS
ID : R01 DA043535
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH104344
Pays : United States
Informations de copyright
Copyright © 2017. Published by Elsevier Inc.
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