ArticleBiological psychiatry2015
Direct regulation of diurnal Drd3 expression and cocaine reward by NPAS2.
Article in Biological psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 108 citations in OpenAlex.
- Sex differences in nucleus accumbens circuitry engaged with binge-like ethanol drinking.Psychopharmacology · 2026Article
- 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
- Nucleus accumbens core chemogenetic excitation in male mice and chemogenetic inhibition in female mice reduced ethanol reward.Biology of sex differences · 2025Article
- A Pocket Guide for the Experimenter Studying Daily Rhythms in Memory-Related Behavior.Current protocols · 2025Article
- Cell-type and sex-specific rhythmic gene expression in the nucleus accumbens.Molecular psychiatry · 2024Article
- Adolescent circadian rhythm disruption increases reward and risk-taking.Frontiers in neuroscience · 2024Article
- Review
- Profiling transcriptomic responses of human stem cell-derived medium spiny neuron-like cells to exogenous phasic and tonic neurotransmitters.Molecular and cellular neurosciences · 2023Article
- Differential Effects of Cocaine and Morphine on the Diurnal Regulation of the Mouse Nucleus Accumbens Proteome.Journal of proteome research · 2023Article
- Dopamine DJournal of medicinal chemistry · 2023Article
- Diurnal Alterations in Gene Expression Across Striatal Subregions in Psychosis.Biological psychiatry · 2023Article
- A role for the circadian transcription factor NPAS2 in the progressive loss of non-rapid eye movement sleep and increased arousal during fentanyl withdrawal in male mice.Psychopharmacology · 2022Article
- Targeting the Maladaptive Effects of Binge Drinking on Circadian Gene Expression.International journal of molecular sciences · 2022Article
- Sex-specific role of the circadian transcription factor NPAS2 in opioid tolerance, withdrawal and analgesia.Genes, brain, and behavior · 2022Article
- Astrocyte Molecular Clock Function in the Nucleus Accumbens Is Important for Reward-Related Behavior.Biological psychiatry · 2022Article
- Neurobiological and behavioral mechanisms of circadian rhythm disruption in bipolar disorder: A critical multi-disciplinary literature review and agenda for future research from the ISBD task force on chronobiology.Bipolar disorders · 2022Review
- Diurnal rhythms in cholinergic modulation of rapid dopamine signals and associative learning in the striatum.Cell reports · 2022Article
- Molecular rhythm alterations in prefrontal cortex and nucleus accumbens associated with opioid use disorder.Translational psychiatry · 2022Article
- Central nucleus of the amygdala projections onto the nucleus accumbens core regulate binge-like alcohol drinking in a CRF-dependent manner.Neuropharmacology · 2022Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundCircadian gene disruptions are associated with the development of psychiatric disorders, including addiction. However, the mechanisms by which circadian genes regulate reward remain poorly understood.
methodsWe used mice with a mutation in Npas2 and adeno-associated virus-short hairpin RNA mediated knockdown of Npas2 and Clock in the nucleus accumbens (NAc). We performed conditioned place preference assays. We utilized cell sorting quantitative real-time polymerase chain reaction, and chromatin immunoprecipitation followed by deep sequencing.
resultsNpas2 mutants exhibit decreased sensitivity to cocaine reward, which is recapitulated with a knockdown of neuronal PAS domain protein 2 (NPAS2) specifically in the NAc, demonstrating the importance of NPAS2 in this region. Interestingly, reducing circadian locomotor output cycles kaput (CLOCK) (a homologue of NPAS2) in the NAc had no effect, suggesting an important distinction in NPAS2 and CLOCK function. Furthermore, we found that NPAS2 expression is restricted to Drd1 expressing neurons while CLOCK is ubiquitous. Moreover, NPAS2 and CLOCK have distinct temporal patterns of DNA binding, and we identified novel and unique binding sites for each protein. We identified the Drd3 dopamine receptor as a direct transcriptional target of NPAS2 and found that NPAS2 knockdown in the NAc disrupts its diurnal rhythm in expression. Chronic cocaine treatment likewise disrupts the normal rhythm in Npas2 and Drd3 expression in the NAc, which may underlie behavioral plasticity in response to cocaine.
conclusionsTogether, these findings identify an important role for the circadian protein, NPAS2, in the NAc in the regulation of dopamine receptor expression and drug reward.
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