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

Serum- and glucocorticoid-inducible kinase 1 activity in ventral tegmental area dopamine neurons regulates cocaine conditioned place preference but not cocaine self-administration

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Doyle, Marie A., Bali, Vedrana, Eagle, Andrew L., Stark, Ali R., Fallon, Barbara, Neve, Rachael L., Robison, A. J., Mazei-Robison, Michelle S.·2021·Neuropsychopharmacology
DOI 10.1038/s41386-021-01032-3PMC PMC8280171
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Abstract

Drugs of abuse regulate the activity of the mesolimbic dopamine (DA) system, and drug-induced changes in ventral tegmental area (VTA) cellular activity and gene regulation are linked to behavioral outputs associated with addiction. Previous work from our lab determined that VTA serum- and glucocorticoid-inducible kinase 1 (SGK1) transcription and catalytic activity were increased by repeated cocaine administration; however, it was unknown if these biochemical changes contributed to cocaine-elicited behaviors. Using transgenic and viral-mediated manipulations, we investigated the role of VTA SGK1 catalytic activity in regulating cocaine conditioned place preference and self-administration. We showed intra-VTA infusion of a catalytically inactive SGK1 mutant (K127Q) significantly decreased cocaine conditioned place preference (CPP). Further, we found that K127Q expression in VTA DA neurons significantly decreased cocaine CPP, while this same manipulation in VTA GABA neurons had no effect. However, blunted VTA DA SGK1 catalytic activity did not alter cocaine self-administration. Altogether, these studies identify the specific VTA cells critical for SGK1-mediated effects on cocaine CPP but not self-administration.

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  • Inactivating VTA SGK1 catalytic activity with inactive SGK1 mutant (K127Q) significantly reduces cocaine-conditioned place preference without altering cocaine-seeking behavior.

    “inactivating VTA SGK1 catalytic activity with an inactive SGK1 mutant (K127Q) significantly reduces cocaine-conditioned place preference without altering cocaine-seeking behavior”

    From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Doyle et al., 2021

    The Results report that VTA K127Q expression significantly reduced cocaine conditioned place preference. They also report no change in cocaine self-administration or motivation to obtain cocaine infusions in male mice. Those tests support the narrower finding, but not an unqualified claim about cocaine-seeking behavior generally. (LLM, conf=0.83)

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Cited by

Sorted by citations

Authors
Doyle, M. A., Bali, V., Eagle, A. L., Stark, A. R., Fallon, B., Neve, R. L., Robison, A. J., & Mazei-Robison, M. S.
Affiliations
  • Michigan State University (US)
  • Massachusetts General Hospital (US)
ORCID
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2021-05-18
Volume
46
Issue
9
Pages
1574-1583
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/s41386-021-01032-3
PMC
PMC8280171
OpenAlex
W3163509755
Cited by
9
References
9
Citations by year
2026: 2 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 2
FWCI
0.69
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuropsychopharmacology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NS044928)
  • U.S. Department of Health & Human Services | NIH | 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
serum- and glucocorticoid-inducible kinase 1, ventral tegmental area, dopaminergic neurons, cocaine conditioned place preference, cocaine self-administration, mesolimbic dopamine system, addiction, GABAergic neurons, viral gene expression
MeSH terms
Cocaine, Conditioning, Classical, Glucocorticoids, Ventral Tegmental Area, Dopaminergic Neurons

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