Behavioral effects of SGK1 knockout in VTA and dopamine neurons
Open accessAbstract
Drugs of abuse cause significant neuroadaptations within the ventral tegmental area (VTA), with alterations in gene expression tied to changes in reward behavior. Serum- and glucocorticoid-inducible kinase 1 (SGK1) transcription, catalytic activity, and phosphorylation are upregulated in the VTA by chronic cocaine or morphine treatment, positioning SGK1 as a critical mediator of reward behavior. Using transgenic mouse models, we investigated the effect of SGK1 knockout in the VTA and in dopamine (DA) neurons to evaluate the necessity of protein expression for natural and drug reward behaviors. SGK1 knockdown in the VTA did not impact reward behaviors. Given VTA cellular heterogeneity, we also investigated a DA neuron-specific SGK1 knockout (KO). DA SGK1 KO significantly decreased body weight of adult mice as well as increased general locomotor activity; however, reward behaviors were similarly unaltered. Given that SGK1 mutants virally overexpressed in the VTA are capable of altering drug-associated behavior, our current results suggest that changes in SGK1 protein signaling may be distinct from expression. This work yields novel information on the impact of SGK1 deletion, critical for understanding the role of SGK1 signaling in the central nervous system and evaluating SGK1 as a potential therapeutic target for treatment of substance use disorders.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Transcription, catalytic activity, and phosphorylation of SGK1 are upregulated in VTA through chronic cocaine or morphine treatment.
“Transcription, catalytic activity, and phosphorylation of SGK1 are upregulated in the VTA through chronic cocaine or morphine treatment”
From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Doyle et al., 2020
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies
Lang, U. E., & Borgwardt, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350094 · Cited by 8,501 · see citing works
Dahlstroem, A., & Fuxé, K. (1964) · PubMed · Cited by 5,143 · see citing works
Frequency Dependence of Signal Power and Spatial Reach of the Local Field Potential
Leski, S., Lindén, H., Tetzlaff, T., Pettersen, K. H., & Einevoll, G. T. (2013) · PubMed Central · doi:10.18154/rwth-conv-084442 · Cited by 3,662 · see citing works
Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter
Giros, B., Jaber, M., Jones, S. R., Wightman, R. M., & Caron, M. G. (1996) · Nature · doi:10.1038/379606a0 · Cited by 2,476 · see citing works
Dopamine neuron systems in the brain: An update
Björklund, A., & Dunnett, S. B. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.03.006 · Cited by 1,777 · see citing works
Swanson, L. W. (1982) · Brain Research Bulletin · doi:10.1016/0361-9230(82)90145-9 · Cited by 1,718 · see citing works
The brain on drugs: from reward to addiction
Volkow, N. D., & Morales, M. (2015) · Cell · doi:10.1016/j.cell.2015.07.046 · Cited by 1,306 · see citing works
The nuts and bolts of AGC protein kinases
Pearce, L. R., Komander, D., & Alessi, D. R. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2822 · Cited by 1,294 · see citing works
Ventral tegmental area: cellular heterogeneity, connectivity and behaviour
Morales, M., & Margolis, E. B. (2017) · Nature reviews. Neuroscience · doi:10.1038/nrn.2016.165 · Cited by 1,108 · see citing works
Striatal Dopamine Release after Amphetamine or Nerve Degeneration Revealed by Rotational Behaviour
Ungerstedt, U. (1971) · Acta Physiologica Scandinavica · doi:10.1111/j.1365-201x.1971.tb10999.x · Cited by 924 · see citing works
Langston, J. W., Forno, L. S., Rebert, C. S., & Irwin, I. (1984) · Brain Research · doi:10.1016/0006-8993(84)90777-7 · Cited by 922 · see citing works
García-Martínez, J. M., & Alessi, D. R. (2008) · Biochemical Journal · doi:10.1042/bj20081668 · Cited by 907 · see citing works
Leptin Receptor Signaling in Midbrain Dopamine Neurons Regulates Feeding
Hommel, J. D., Trinko, R., Sears, R. M., Georgescu, D., Liu, Z.-W., Gao, X.-B., Thurmon, J. J., Marinelli, M., & DiLeone, R. J. (2006) · Neuron · doi:10.1016/j.neuron.2006.08.023 · Cited by 902 · see citing works
Brunet, A., Park, J., Tran, H., Hu, L. S., Hemmings, B. A., & Greenberg, M. E. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.3.952-965.2001 · Cited by 860 · see citing works
Sgk1-Dependent Stimulation of Cardiac Na+/H+Exchanger Nhe1 by Dexamethasone
Voelkl, J. G. J., Pasham, V., Ahmed, M. S. E., Walker, B., Szteyn, K., Kuhl, D., Metzler, B., Alesutan, I., & Lang, F. J. W. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350120 · Cited by 859 · see citing works
Reward and aversion in a heterogeneous midbrain dopamine system
Lammel, S., Lim, B. K., & Malenka, R. C. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.03.019 · Cited by 804 · see citing works
(Patho)physiological Significance of the Serum- and Glucocorticoid-Inducible Kinase Isoforms
Lang, F., Böhmer, C., Palmada, M., Seebohm, G., Strutz-Seebohm, N., & Vallon, V. (2006) · Physiological Reviews · doi:10.1152/physrev.00050.2005 · Cited by 689 · see citing works
Nair‐Roberts, R. G., Chatelain-Badie, S. D., Benson, E. M., White‐Cooper, H., Bolam, J. P., & Ungless, M. A. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.01.046 · Cited by 653 · see citing works
Kobayashi, T., & Cohen, P. (1999) · Biochemical Journal · doi:10.1042/bj3390319 · Cited by 614 · see citing works
Park, J., Leong, M., Buse, P., Maiyar, A. C., Firestone, G. L., & Hemmings, B. (1999) · EMBO Journal · doi:10.1093/emboj/18.11.3024 · Cited by 588 · see citing works
Webster, M. K., Goya, L., Ge, Y., Maiyar, A. C., & Firestone, G. L. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.4.2031-2040.1993 · Cited by 581 · see citing works
Dopaminergic dynamics underlying sex-specific cocaine reward
Calipari, E. S., Juarez, B., Morel, C., Walker, D. M., Cahill, M. E., Ribeiro, E., Roman-Ortiz, C., Ramakrishnan, C., Deisseroth, K., Han, M.-H., et al. (2017) · Nature Communications · doi:10.1038/ncomms13877 · Cited by 359 · see citing works
Impaired renal Na+ retention in the sgk1-knockout mouse
Wulff, P., Vallon, V., Huang, D. Y., Völkl, H., Yu, F., Richter, K., Jansen, M., Schlünz, M., Klingel, K., Loffing, J., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15696 · Cited by 353 · see citing works
Murray, J. T., CAMPBELL, D. G., Morrice, N. A., Auld, G. C., Shpiro, N., Márquez, R., Peggie, M. W., Bain, J., Bloomberg, G. B., Grahammer, F., et al. (2004) · Biochemical Journal · doi:10.1042/bj20041057 · Cited by 341 · see citing works
The Molecular Basis of Drug Addiction: Linking Epigenetic to Synaptic and Circuit Mechanisms
Nestler, E. J., & Lüscher, C. (2019) · Neuron · doi:10.1016/j.neuron.2019.01.016 · Cited by 331 · see citing works
Mechanisms for acute stress-induced enhancement of glutamatergic transmission and working memory
Yuen, E. Y., Liu, W., Karatsoreos, I. N., Ren, Y., Feng, J., McEwen, B. S., & Yan, Z. (2011) · Molecular Psychiatry · doi:10.1038/mp.2010.50 · Cited by 324 · see citing works
Shippenberg, T. S., & Heidbreder, C. A. (1995) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)09578-3 · Cited by 263 · see citing works
Marinelli, M., & White, F. J. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-23-08876.2000 · Cited by 254 · see citing works
Loss of autoreceptor functions in mice lacking the dopamine transporter
Jones, S. R., Gainetdinov, R. R., Hu, X., Cooper, D., Wightman, R. M., White, F. J., & Caron, M. G. (1999) · Nature Neuroscience · doi:10.1038/10204 · Cited by 247 · see citing works
Hypothalamic arcuate nucleus tyrosine hydroxylase neurons play orexigenic role in energy homeostasis
Zhang, X., & van den Pol, A. N. (2016) · Nature Neuroscience · doi:10.1038/nn.4372 · Cited by 205 · see citing works
Sex differences in the conditioned rewarding effects of cocaine
Russo, S. J., Jenab, S., Fabian, S. J., Festa, E. D., Kemen, L. M., & Quiñones-Jenab, V. (2003) · Brain Research · doi:10.1016/s0006-8993(03)02346-1 · Cited by 182 · see citing works
Krishnan, V., Han, M.-H., Mazei-Robison, M., Iñiguez, S. D., Ables, J. L., Vialou, V., Berton, O., Ghose, S., Covington, H. E., Wiley, M. D., et al. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.06.003 · Cited by 176 · see citing works
Self-citationDiversity of Dopaminergic Neural Circuits in Response to Drug Exposure
Juarez, B., & Han, M. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.32 · Cited by 165 · see citing works
McClung, C. A., Nestler, E. J., & Zachariou, V. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.0062-05.2005 · Cited by 163 · see citing works
Nichols, C. (2002) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00405-5 · Cited by 163 · see citing works
The dissection of transcriptional modules regulated by various drugs of abuse in the mouse striatum
Piechota, M., Korostyński, M., Solecki, W., Gieryk, A., Ślęzak, M., Bilecki, W., Ziółkowska, B., Kostrzewa, E., Cymerman, I. A., Swiech, L. J., et al. (2010) · Genome biology · doi:10.1186/gb-2010-11-5-r48 · Cited by 159 · see citing works
Elevated SGK1 predicts resistance of breast cancer cells to Akt inhibitors
Sommer, E. M., Dry, H., Cross, D. A. E., Guichard, S. M., Davies, B. R., & Alessi, D. R. (2013) · Biochemical Journal · doi:10.1042/bj20130342 · Cited by 158 · see citing works
Epithelial Na+channel activation and processing in mice lacking SGK1
Fejes‐Tóth, G., Frindt, G., Náray‐Fejes‐Tóth, A., & Palmer, L. G. (2008) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00579.2007 · Cited by 132 · see citing works
Self-citationHayashi, M., Tapping, R. I., Chao, T.-H., Lo, J., King, C. C., Yang, Y. C., & Lee, J.-D. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c000838200 · Cited by 130 · see citing works
Tsai, K., Chen, S., Ma, Y., Hsu, W., & Lee, E. H. Y. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.062405399 · Cited by 103 · see citing works
Cristofano, A. D. (2016) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2016.11.006 · Cited by 101 · see citing works
Voluntary consumption of morphine in 15 inbred mouse strains
Belknap, J. K., Crabbe, J. C., Riggan, J. P., & O’Toole, L. A. (1993) · Psychopharmacology · doi:10.1007/bf02244932 · Cited by 96 · see citing works
Lee, E. H. Y., Hsu, W., Ma, Y., Lee, P. J., & Chao, C.-C. (2003) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2003.03032.x · Cited by 90 · see citing works
Mu‐opioid receptor activation induces transcriptional plasticity in the central extended amygdala
Befort, K., Filliol, D., Ghate, A., Darcq, E., Matifas, A., Muller, J., Lardenois, A., Thibault-Carpentier, C., Dembélé, D., Merrer, J. L., et al. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06273.x · Cited by 89 · see citing works
Economic costs of drug abuse: Financial, cost of illness, and services
Cartwright, W. S. (2007) · Journal of Substance Abuse Treatment · doi:10.1016/j.jsat.2007.04.003 · Cited by 80 · see citing works
Licznerski, P., Duric, V., Banasr, M., Alavian, K. N., Ota, K. T., Kang, H. J., Jonas, E. A., Ursano, R., Krystal, J. H., Duman, R. S., et al. (2015) · PLOS Biology · doi:10.1371/journal.pbio.1002282 · Cited by 79 · see citing works
Akt Mediates Insulin-stimulated Phosphorylation of Ndrg2
Burchfield, J. G., Lennard, A. J., Narasimhan, S. R., Hughes, W. E., Wasinger, V. C., Corthals, G. L., Okuda, T., Kondoh, H., Biden, T. J., & Schmitz‐Peiffer, C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m401504200 · Cited by 79 · see citing works
Reducing Ventral Tegmental Dopamine D2 Receptor Expression Selectively Boosts Incentive Motivation
de Jong, J. W., Roelofs, T. J. M., Mol, F., Hillen, A. E. J., Meijboom, K. E., Luijendijk, M. C. M., van der Eerden, H. A. M., Garner, K. M., Vanderschuren, L. J. M. J., & Adan, R. A. H. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.60 · Cited by 77 · see citing works
Brabant, C., Quertemont, É., & Tirelli, E. (2005) · Psychopharmacology · doi:10.1007/s00213-004-2138-6 · Cited by 72 · see citing works
Contributions of taste factors and gender to opioid preference in C57BL and DBA mice
Forgie, M. L., Beyerstein, B. L., & Alexander, B. K. (1988) · Psychopharmacology · doi:10.1007/bf00174516 · Cited by 64 · see citing works
Cyclin-Dependent Kinase 5 in the Ventral Tegmental Area Regulates Depression-Related Behaviors
Zhong, P., Liu, X., Zhang, Z., Hu, Y. C., Liu, S. J., Lezama-Ruiz, M., Joksimovic, M., & Liu, Q.-S. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.3673-13.2014 · Cited by 53 · see citing works
SGK protein kinase facilitates the expression of long-term potentiation in hippocampal neuronsPreprint
Ma, Y., Tsai, M., Hsu, W., & Lee, E. H. Y. (2006) · Learning & Memory · doi:10.1101/lm.179206 · Cited by 49 · see citing works
Large-scale analysis of glucocorticoid target genes in rat hypothalamus
Sato, H., Horikawa, Y., Iizuka, K., Sakurai, N., Tanaka, T., Shihara, N., Oshima, A., Takeda, J., & Mikuni, M. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05489.x · Cited by 46 · see citing works
Lee, C., Tyan, S., Ma, Y., Tsai, M., Yang, Y. C., & Lee, E. H. Y. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04650.x · Cited by 40 · see citing works
Cooper, S., Kechner, M., Caraballo-Pérez, D., Kaska, S., Robison, A. J., & Mazei‐Robison, M. S. (2017) · Scientific Reports · doi:10.1038/s41598-017-09106-3 · Cited by 38 · see citing works
Self-citationFischer, S. J., Arguello, A. A., Charlton, J. L., Fuller, D. C., Zachariou, V., & Eisch, A. J. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.11.035 · Cited by 37 · see citing works
Gao, P., Limpens, J. H. W., Spijker, S., Vanderschuren, L. J. M. J., & Voorn, P. (2015) · Addiction Biology · doi:10.1111/adb.12330 · Cited by 37 · see citing works
Lee, C. T., Ma, Y. L., & Lee, E. H. Y. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04284.x · Cited by 32 · see citing works
SGK1/FOXO3 Signaling in Hypothalamic POMC Neurons Mediates Glucocorticoid-Increased Adiposity
Deng, Y., Xiao, Y., Yuan, F., Liu, Y., Jiang, X., Deng, J., Fejes‐Tóth, G., Náray‐Fejes‐Tóth, A., Chen, S., Chen, Y., et al. (2018) · Diabetes · doi:10.2337/db17-1069 · Cited by 31 · see citing works
Self-citationTyan, S., Tsai, M., Lin, C., Ma, Y., & Lee, E. H. Y. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.05186.x · Cited by 31 · see citing works
Heller, E. A., Kaska, S., Fallon, B., Ferguson, D., Kennedy, P., Neve, R. L., Nestler, E. J., & Mazei‐Robison, M. S. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12925 · Cited by 30 · see citing works
Self-citationSimmons, S. C., Wheeler, K., & Mazei‐Robison, M. S. (2019) · Molecular Brain · doi:10.1186/s13041-019-0435-6 · Cited by 27 · see citing works
Self-citationSun, H., Calipari, E. S., Beveridge, T. J. R., Jones, S. R., & Chen, R. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.08.053 · Cited by 19 · see citing works
Deletion of Rictor in catecholaminergic neurons alters locomotor activity and ingestive behavior
Kaska, S., Brunk, R., Bali, V., Kechner, M., & Mazei‐Robison, M. S. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.02.001 · Cited by 8 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Costa, K. M., Schenkel, D., & Roeper, J. (2021) · Scientific Reports · doi:10.1038/s41598-021-82600-x · Cited by 31 · see citing works
Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain
Howard, P. G., Zou, P., Zhang, Y., Huang, F., Tesic, V., Wu, C. Y.-C., & Lee, R. H.-C. (2024) · Experimental Neurology · doi:10.1016/j.expneurol.2024.114973 · Cited by 13 · see citing works
The role of serum/glucocorticoid-regulated kinase 1 in brain function following cerebral ischemia
Wu, C. Y., Zhang, Y., Xu, L., Huang, Z., Zou, P., Clemons, G. A., Li, C., Citadin, C. T., Zhang, Q., & Lee, R. H. (2024) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x231224508 · Cited by 12 · see citing works
Doyle, M. A., Bali, V., Eagle, A. L., Stark, A. R., Fallon, B., Neve, R. L., Robison, A. J., & Mazei-Robison, M. S. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-021-01032-3 · Cited by 9 · see citing works
Self-citationZhang, X., Gao, H., Chen, X., Liu, Z., Wang, H., Cui, M., Yu, Y., Yu, Y., Chen, S., Xing, X., et al. (2024) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2024.135583 · Cited by 8 · see citing works
Doyle, M. A., Salimando, G. J., Altemus, M. E., Badt, J. K., Bedenbaugh, M. N., Vardy, A. S., Adank, D. N., Park, A. S., & Winder, D. G. (2024) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.15432 · Cited by 3 · see citing works
Self-citationQuiles, C. R., Simmons, S. C., Dodson, O., Alday, M., Fontánez, N. C., Caico, S., Garrison, A., Shafieichaharberoud, F., Huang, X., Hu, Q., et al. (2025) · Journal of Neuroscience · doi:10.1523/jneurosci.1662-24.2025 · Cited by 3 · see citing works
Self-citationSu, Y., Wang, B., Ye, J., Wang, Y., Cui, Y., Chen, C., Ruan, N., Hu, Z., Li, L., Liu, H., et al. (2022) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2022.11.070 · Cited by 1 · see citing works
Grad, M., Volkov, H., & Shomron, N. (2026) · Journal of Molecular Neuroscience · doi:10.1007/s12031-026-02597-8
- Authors
- Doyle, M. A., Stark, A. R., Fejes-Tóth, G., Náray-Fejes-Tóth, A., & Mazei-Robison, M. S.
- Affiliations
- Michigan State University (US)
- Venue
- Scientific Reports
- Published
- 2020-09-08
- Volume
- 10
- Issue
- 1
- Pages
- 14751-14751
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC7478959
- OpenAlex
- W3084377766
- Cited by
- 9
- References
- 64
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2022: 1 · 2021: 2
- FWCI
- 0.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS044928)
- National Institute on Drug Abuse (DA039895)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- SGK1, serum- and glucocorticoid-inducible kinase 1, ventral tegmental area, dopaminergic neurons, drug reward, cocaine, morphine, locomotor activity, body weight, substance use disorders, viral overexpression, neural adaptation
- MeSH terms
- Serum-Glucocorticoid Regulated Kinases, Animals, Behavior, Animal, Cocaine, Female, Male, Mice, Inbred C57BL, Reward, Signal Transduction, Protein Serine-Threonine Kinases, Ventral Tegmental Area, Immediate-Early Proteins, Mice, Knockout, Dopamine Uptake Inhibitors, Mice, Dopaminergic Neurons
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review