ArticleNeuropharmacology2017
The effects of reduced dopamine transporter function and chronic lithium on motivation, probabilistic learning, and neurochemistry in mice: Modeling bipolar mania.
Article in Neuropharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.
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Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 37 citations in OpenAlex.
- The Impact of Cannabis Use on Cognition in People with HIV: Evidence of Function-Dependent Effects and Mechanisms from Clinical and Preclinical Studies.Current HIV/AIDS reports · 2024Pooled it
- Dopamine transporter knockdown mice in the behavioral pattern monitor: A robust, reproducible model for mania-relevant behaviors.Pharmacology, biochemistry, and behavior · 2019Pooled it
- Vitamin A deficiency induces sex-specific reward processing alterations through a dysregulation of the mesolimbic dopamine transmission in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Chemogenetic inhibition of the anterior cingulate cortex increases safe decision-making in aged mice performing the Iowa Gambling Task.Psychopharmacology · 2026Article
- A ventral tegmental area GABAergic projection to the ventral pallidum regulates value-based decision making in mice.bioRxiv : the preprint server for biology · 2026Article
- Computational modeling of reversal learning impairments in schizophrenia and bipolar disorder reveals shared failure to exploit rewards.Journal of psychopathology and clinical science · 2025Article
- Sex-dependent differences in the ability of nicotine to modulate discrimination learning and cognitive flexibility in mice.Journal of neurochemistry · 2025Article
- Activity in the Dorsomedial Striatum Underlies Serial Reversal Learning Performance Under Probabilistic Uncertainty.Biological psychiatry global open science · 2023Article
- Bipolar spectrum disorders in neurologic disorders.Frontiers in psychiatry · 2022Review
- Inhibition of glycogen synthase kinase 3 by lithium, a mechanism in search of specificity.Frontiers in molecular neuroscience · 2022Review
- Valproate reverses mania-like behaviors in mice via preferential targeting of HDAC2.Molecular psychiatry · 2021Article
- Enlightened: addressing circadian and seasonal changes in photoperiod in animal models of bipolar disorder.Translational psychiatry · 2021Review
- The effects of early life stress on motivated behaviors: A role for gonadal hormones.Neuroscience and biobehavioral reviews · 2020Review
- Converging evidence that short-active photoperiod increases acetylcholine signaling in the hippocampus.Cognitive, affective & behavioral neuroscience · 2020Article
- Neurobehavioral changes arising from early life dopamine signaling perturbations.Neurochemistry international · 2020Review
- Short-active photoperiod gestation induces psychiatry-relevant behavior in healthy mice but a resiliency to such effects are seen in mice with reduced dopamine transporter expression.Scientific reports · 2020Article
- Oxytocin improves probabilistic reversal learning but not effortful motivation in Brown Norway rats.Neuropharmacology · 2019Article
- Separating Probability and Reversal Learning in a Novel Probabilistic Reversal Learning Task for Mice.Frontiers in behavioral neuroscience · 2019Article
- Nicotine improves probabilistic reward learning in wildtype but not alpha7 nAChR null mutants, yet alpha7 nAChR agonists do not improve probabilistic learning.European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2018Article
- Translational Assessments of Reward and Anhedonia: A Tribute to Athina Markou.Biological psychiatry · 2018Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundBipolar disorder (BD) mania patients exhibit poor cognition and reward-seeking/hypermotivation, negatively impacting a patient's quality of life. Current treatments (e.g., lithium), do not treat such deficits. Treatment development has been limited due to a poor understanding of the neural mechanisms underlying these behaviors. Here, we investigated putative mechanisms underlying cognition and reward-seeking/motivational changes relevant to BD mania patients using two validated mouse models and neurochemical analyses.
methodsThe effects of reducing dopamine transporter (DAT) functioning via genetic (knockdown vs. wild-type littermates), or pharmacological (GBR12909- vs. vehicle-treated C57BL/6J mice) means were assessed in the probabilistic reversal learning task (PRLT), and progressive ratio breakpoint (PRB) test, during either water or chronic lithium treatment. These tasks quantify reward learning and effortful motivation, respectively. Neurochemistry was performed on brain samples of DAT mutants ± chronic lithium using high performance liquid chromatography.
resultsReduced DAT functioning increased reversals in the PRLT, an effect partially attenuated by chronic lithium. Chronic lithium alone slowed PRLT acquisition. Reduced DAT functioning increased motivation (PRB), an effect attenuated by lithium in GBR12909-treated mice. Neurochemical analyses revealed that DAT knockdown mice exhibited elevated homovanillic acid levels, but that lithium had no effect on these elevated levels.
conclusionsReducing DAT functioning recreates many aspects of BD mania including hypermotivation and improved reversal learning (switching), as well as elevated homovanillic acid levels. Chronic lithium only exerted main effects, impairing learning and elevating norepinephrine and serotonin levels of mice, not specifically treating the underlying mechanisms identified in these models.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.