ArticleBiological psychiatry2010
Knockdown of Clock in the ventral tegmental area through RNA interference results in a mixed state of mania and depression-like behavior.
Article in Biological psychiatry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers, 2 of them syntheses that pooled it.
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Who cites it
139 citing papers in PubMed, 2 syntheses or guidelines pooled it, 243 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
- Pooled it
- Modulation of neuronal excitability and plasticity by BHLHE41 conveys lithium non-responsiveness.Molecular psychiatry · 2026Article
- Conative inference as a mechanism of allostatic resilience: wanting to be and being to want.Cognitive, affective & behavioral neuroscience · 2026Review
- Cell-type targeted CRISPR/Cas9 Clock knockdown in mouse VTA dopamine neurons alter sleep, behavior, and cellular excitability.bioRxiv : the preprint server for biology · 2026Article
- Gut microbiota modulates synaptic plasticity, connectivity, and dopamine transmission in the VTA-mPFC pathway in bipolar depression.Molecular psychiatry · 2026Article
- Circadian modulation of spontaneous dopamine release shapes reward-evoked signaling in the nucleus accumbens.bioRxiv : the preprint server for biology · 2026Article
- Reconceptualizing bipolar disorder through an integrative biological lens: synthesis, convergence, and emerging directions.Frontiers in integrative neuroscience · 2026Review
- Tonic dopamine sensing reveals a D2 and D3-mediated dopamine response to raclopride inNpj biosensing · 2026Article
- Tonic Dopamine Sensing Reveals a D2/D3 Mediated Dopamine Response to Raclopride in ClockΔ19 Mice Model.Research square · 2025Article
- Microglia-mediated inflammation and synaptic pruning contribute to sleep deprivation-induced mania in a sex-specific manner.Translational psychiatry · 2025Article
- Knockout of Bmal1 in dopaminergic neurons induces ADHD-like symptoms via hyperactive dopamine signaling in male mice.Behavioral and brain functions : BBF · 2025Article
- Suprachiasmatic nucleus dysfunction induces anxiety- and depression-like behaviors via activating the BDNF-TrkB pathway of the striatum.Translational psychiatry · 2025Article
- Insomnia in Parkinson's Disease: Causes, Consequences, and Therapeutic Approaches.Molecular neurobiology · 2025Review
- The molecular clock drives motivated locomotion and time-of-day-dependent firing patterns in mouse dopaminergic neurons.Npj biological timing and sleep · 2025Article
- Beyond vision: effects of light on the circadian clock and mood-related behaviours.Npj biological timing and sleep · 2025Review
- Decoding serotonin: the molecular symphony behind depression.Frontiers in cellular neuroscience · 2025Review
- Sleep and circadian disruption in bipolar disorders: From psychopathology to digital phenotyping in clinical practice.Psychiatry and clinical neurosciences · 2024Review
- Role of the circadian nuclear receptor REV-ERBα in dorsal raphe serotonin synthesis in mood regulation.Communications biology · 2024Article
- Impact of Serotonin Deficiency on Circadian Dopaminergic Rhythms.International journal of molecular sciences · 2024Article
79 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundCircadian rhythm abnormalities are strongly associated with bipolar disorder; however the role of circadian genes in mood regulation is unclear. Previously, we reported that mice with a mutation in the Clock gene (ClockDelta19) display a behavioral profile that is strikingly similar to bipolar patients in the manic state.
methodsHere, we used RNA interference and viral-mediated gene transfer to knock down Clock expression specifically in the ventral tegmental area (VTA) of mice. We then performed a variety of behavioral, molecular, and physiological measures.
resultsWe found that knockdown of Clock, specifically in the VTA, results in hyperactivity and a reduction in anxiety-related behavior, which is similar to the phenotype of the ClockDelta19 mice. However, VTA-specific knockdown also results in a substantial increase in depression-like behavior, creating an overall mixed manic state. Surprisingly, VTA knockdown of Clock also altered circadian period and amplitude, suggesting a role for Clock in the VTA in the regulation of circadian rhythms. Furthermore, VTA dopaminergic neurons expressing the Clock short hairpin RNA have increased activity compared with control neurons, and this knockdown alters the expression of multiple ion channels and dopamine-related genes in the VTA that could be responsible for the physiological and behavioral changes in these mice.
conclusionsTaken together, these results suggest an important role for Clock in the VTA in the regulation of dopaminergic activity, manic and depressive-like behavior, and circadian rhythms.
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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.