ArticleMolecular psychiatry2014
An important role for cholecystokinin, a CLOCK target gene, in the development and treatment of manic-like behaviors.
Article in Molecular psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Face and predictive validity of the ClockΔ19 mouse as an animal model for bipolar disorder: a systematic review.Molecular psychiatry · 2018Pooled it
- A Chrono-Metabolic Approach to Mental Health: Current Perspectives on Circadian Rhythms, Gut Microbiota, and Microbial Metabolites in Mood Disorders.Metabolites · 2026Review
- Gut microbiota modulates synaptic plasticity, connectivity, and dopamine transmission in the VTA-mPFC pathway in bipolar depression.Molecular psychiatry · 2026Article
- CCK2R regulates METH-induced CPP acquisition within VTA-BLA-BNST circuit in male mice.Translational psychiatry · 2026Article
- Optimizing Chronotherapy in Psychiatric Care: The Impact of Circadian Rhythms on Medication Timing and Efficacy.Clocks & sleep · 2024Review
- Impact of Serotonin Deficiency on Circadian Dopaminergic Rhythms.International journal of molecular sciences · 2024Article
- Microarray evidence that 8-cell human embryos express some hormone family members including oxytocin.Journal of assisted reproduction and genetics · 2024Article
- Mood and behavior regulation: interaction of lithium and dopaminergic system.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
- Emotionally clocked out: cell-type specific regulation of mood and anxiety by the circadian clock system in the brain.Frontiers in molecular neuroscience · 2023Review
- Mood phenotypes in rodent models with circadian disturbances.Neurobiology of sleep and circadian rhythms · 2022Review
- The trilateral interactions between mammalian target of rapamycin (mTOR) signaling, the circadian clock, and psychiatric disorders: an emerging model.Translational psychiatry · 2022Review
- The Neuromodulatory Basis of Aggression: Lessons From the Humble Fruit Fly.Frontiers in behavioral neuroscience · 2022Review
- Molecular Targets of Cannabinoids Associated with Depression.Current medicinal chemistry · 2022Review
- Valproate reverses mania-like behaviors in mice via preferential targeting of HDAC2.Molecular psychiatry · 2021Article
- Valproate Reverses Mania-Like Behavior ofNeuropsychiatric disease and treatment · 2021Article
- Circadian Rhythms and the Gastrointestinal Tract: Relationship to Metabolism and Gut Hormones.Endocrinology · 2020Review
- Neuropeptides Modulate Local Astrocytes to Regulate Adult Hippocampal Neural Stem Cells.Neuron · 2020Article
- Mesocortical BDNF signaling mediates antidepressive-like effects of lithium.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Article
- A neuropeptide regulates fighting behavior ineLife · 2020Article
- Circadian rhythm disruption and mental health.Translational psychiatry · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Mice with a mutation in the Clock gene (ClockΔ19) have been identified as a model of mania; however, the mechanisms that underlie this phenotype, and the changes in the brain that are necessary for lithium's effectiveness on these mice remain unclear. Here, we find that cholecystokinin (Cck) is a direct transcriptional target of CLOCK and levels of Cck are reduced in the ventral tegmental area (VTA) of ClockΔ19 mice. Selective knockdown of Cck expression via RNA interference in the VTA of wild-type mice produces a manic-like phenotype. Moreover, chronic treatment with lithium restores Cck expression to near wild-type and this increase is necessary for the therapeutic actions of lithium. The decrease in Cck expression in the ClockΔ19 mice appears to be due to a lack of interaction with the histone methyltransferase, MLL1, resulting in decreased histone H3K4me3 and gene transcription, an effect reversed by lithium. Human postmortem tissue from bipolar subjects reveals a similar increase in Cck expression in the VTA with mood stabilizer treatment. These studies identify a key role for Cck in the development and treatment of mania, and describe some of the molecular mechanisms by which lithium may act as an effective antimanic agent.
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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.