Cited by 9Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchNeuropeptides and Animal Physiology

Behavioral effects of SGK1 knockout in VTA and dopamine neurons

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Doyle, Marie A., Stark, Ali R., Fejes-Tóth, Geza, Náray-Fejes-Tóth, Aniko, Mazei-Robison, Michelle S.·2020·Scientific Reports

Abstract

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.

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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)
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
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

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