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Direct Regulation of Diurnal Drd3 Expression and Cocaine Reward by NPAS2
Open accessAbstract
Background Circadian gene disruptions are associated with the development of psychiatric disorders, including addiction. However, the mechanisms by which circadian genes regulate reward remain poorly understood.Methods We 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.Results Npas2 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.Conclusions Together, 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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“circadian genes in other brain regions outside of this central pace-maker also contribute locally to the control of neuronal metabolism, neurotransmitter synthesis and activity, and the disruption of these functions might contribute to brain disorders264,304–315”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [309]
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Cites
BEDTools: a flexible suite of utilities for comparing genomic features
Quinlan, A. R., & Hall, I. M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq033 · Cited by 27,437
Molecular components of the mammalian circadian clock
Ko, C. H., & Takahashi, J. S. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl207 · Cited by 1,725
Is there a common molecular pathway for addiction?
Nestler, E. J. (2005) · Nature Neuroscience · doi:10.1038/nn1578 · Cited by 1,388
Cell type-specific loss of BDNF signaling mimics optogenetic control of cocaine reward
Lobo, M. K., Covington, H. E., Chaudhury, D., Friedman, A. K., Sun, H., Damez-Werno, D., Dietz, D. M., Zaman, S., Koo, J. W., Kennedy, P. J., et al. (2010) · Science · doi:10.1126/science.1188472 · Cited by 880
Mania-like behavior induced by disruption of CLOCK
Roybal, K., Theobold, D., Graham, A., DiNieri, J. A., Russo, S. J., Krishnan, V., Chakravarty, S., Peevey, J., Oehrlein, N., Birnbaum, S., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0609625104 · Cited by 803
Self-citationCoordinated Expression of Dopamine Receptors in Neostriatal Medium Spiny Neurons
Surmeier, D. J., Song, W., & Yan, Z. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-20-06579.1996 · Cited by 762
Bryne, J. C., Valen, E., Tang, M. E., Marstrand, T. T., Winther, O., da Piedade, I., Krogh, A., Lenhard, B., & Sandelin, A. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm955 · Cited by 702
The “other” circadian system: food as a Zeitgeber
Stephan, F. K. (2002) · Journal of Biological Rhythms · doi:10.1177/074873002129002591 · Cited by 672
Gerfen, C. R., Paletzki, R., & Heintz, N. (2013) · Neuron · doi:10.1016/j.neuron.2013.10.016 · Cited by 647
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McClung, C. A., & Nestler, E. J. (2003) · Nature Neuroscience · doi:10.1038/nn1143 · Cited by 625
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Spanagel, R., Pendyala, G., Abarca, C., Zghoul, T., Sanchis-Segura, C., Magnone, M. C., Lascorz, J., Depner, M., Holzberg, D., Soyka, M., et al. (2005) · Nature Medicine · doi:10.1038/nm1163 · Cited by 594
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Reick, M., Garcia, J. A., Dudley, C., & McKnight, S. L. (2001) · Science · doi:10.1126/science.1060699 · Cited by 572
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McClung, C. A., Sidiropoulou, K., Vitaterna, M., Takahashi, J. S., White, F. J., Cooper, D. C., & Nestler, E. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503584102 · Cited by 493
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Bailey, T. L., & Machanick, P. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks433 · Cited by 472
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Abarca, C., Albrecht, U., & Spanagel, R. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.142039099 · Cited by 472
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DeBruyne, J. P., Noton, E., Lambert, C. M., Maywood, E. S., Weaver, D. R., & Reppert, S. M. (2006) · Neuron · doi:10.1016/j.neuron.2006.03.041 · Cited by 430
Altered patterns of sleep and behavioral adaptability in NPAS2-deficient mice
Dudley, C. A., Erbel-Sieler, C., Estill, S. J., Reick, M., Franken, P., Pitts, S., & McKnight, S. L. (2003) · Science · doi:10.1126/science.1082795 · Cited by 415
UniPROBE: an online database of protein binding microarray data on protein-DNA interactions
Newburger, D. E., & Bulyk, M. L. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn660 · Cited by 376
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David, M., Dzamba, M., Lister, D., Ilie, L., & Brudno, M. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr046 · Cited by 348
Mukherjee, S., Coque, L., Cao, J., Kumar, J., Chakravarty, S., Asaithamby, A., Graham, A., Gordon, E., Enwright, J. F., Dileone, R., et al. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.04.031 · Cited by 249
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Garcia, J. A., Zhang, D., Estill, S. J., Michnoff, C. H., Rutter, J. P., Reick, M., Scott, K., Diaz-Arrastia, R. R., & McKnight, S. L. (2000) · Science · doi:10.1126/science.288.5474.2226 · Cited by 242
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Marcellino, D. J., Ferré, S., Casadó, V., Cortés, A., Foll, B. L., Mazzola, C., Drago, F., Saur, O., Stark, H., Soriano, A., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m710349200 · Cited by 232
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Yujnovsky, I., Hirayama, J., Doi, M., Borrelli, E., & Sassone‐Corsi, P. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510691103 · Cited by 201
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Logan, R. W., Williams, W. P., & McClung, C. A. (2014) · Behavioral Neuroscience · doi:10.1037/a0036268 · Cited by 142
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Imbesi, M., Yildiz, S., Arslan, A. D., Sharma, R., Manev, H., & Uz, T. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.10.044 · Cited by 141
Maywood, E. S., Fraenkel, E., McAllister, C., Wood, N. I., Reddy, A. B., Hastings, M. H., & Morton, A. J. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1694-10.2010 · Cited by 138
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Song, R., Yang, R., Wu, N., Su, R., Li, J., Peng, X., Li, X., Gaál, J., Xi, Z., & Gardner, E. L. (2011) · Addiction Biology · doi:10.1111/j.1369-1600.2011.00317.x · Cited by 96
Lynch, W. J., Girgenti, M. J., Breslin, F. J., Newton, S. S., & Taylor, J. R. (2008) · Brain Research · doi:10.1016/j.brainres.2008.02.106 · Cited by 87
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Higley, A. E., Kiefer, S. W., Li, X., Gaál, J., Xi, Z., & Gardner, E. L. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2011.02.046 · Cited by 70
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Fiorentini, C., Busi, C., Spano, P., & Missale, C. (2009) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2009.09.008 · Cited by 68
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Kosobud, A., Gillman, A. G., Leffel, J. K., Pecoraro, N. C., Rebec, G. V., & Timberlake, W. D. (2007) · The Scientific World JOURNAL · doi:10.1100/tsw.2007.234 · Cited by 66
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Sokoloff, P., Foll, B. L., Perachon, S., Bordet, R., Ridray, S., & Schwartz, J.-C. (2001) · Neurotoxicity Research · doi:10.1007/bf03033202 · Cited by 51
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Harms, E., Young, M. W., & Saez, L. (2003) · Novartis Foundation Symposia · doi:10.1002/0470090839.ch19 · Cited by 27 · cited 1×
“This feedback loop cycles over a twenty-four hour period (6).”
BackgroundBurger, L. Y., & Martin-Iverson, M. T. (1993) · Synapse · doi:10.1002/syn.890130104 · Cited by 9
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Enwright, J. F., Wald, M., Paddock, M., Hoffman, E., Arey, R. N., Edwards, S., Spencer, S. M., Nestler, E. J., & McClung, C. A. (2010) · Brain Research · doi:10.1016/j.brainres.2010.02.081 · Cited by 5
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Metadata
- Authors
- Ozburn, A. R., Falcon, E., Twaddle, A., Nugent, A. L., Gillman, A. G., Spencer, S. M., Arey, R. N., Mukherjee, S., Lyons-Weiler, J., Self, D. W., & McClung, C. A.
- Affiliations
- University of Pittsburgh (US)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- McClung, Colleen A.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 77
- Issue
- 5
- Pages
- 425-433
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC4315729
- OpenAlex
- W1998157722
- Cited by
- 110
- References
- 46
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 6 · 2023: 8 · 2022: 11 · 2021: 6 · 2020: 25 · 2019: 6 · 2018: 12 · 2017: 12 · 2016: 8 · 2015: 4
- FWCI
- 3.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression Young Investigator Award and National Institutes of Health (DA07290, RR024153, DA028085, MH082876, DA023988)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- NPAS2, cocaine reward, circadian rhythm, nucleus accumbens, clocks, transcriptional regulation, diurnal gene expression, addiction, transcription factor binding sites
- MeSH terms
- Animals, Circadian Rhythm, Cocaine, Conditioning, Psychological, Mice, Inbred C57BL, Mice, Transgenic, Nerve Tissue Proteins, Neurons, Nucleus Accumbens, Reward, Space Perception, Receptors, Dopamine D1, Dopamine Uptake Inhibitors, Receptors, Dopamine D3, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, CLOCK Proteins
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