Morphine and cocaine increase serum- and glucocorticoid-inducible kinase 1 activity in the ventral tegmental area

Elizabeth A. Heller, Sophia Kaska, Barbara Fallon, Deveroux Ferguson, Pamela J. Kennedy, Rachael L. Neve, Eric J. Nestler, Michelle S. Mazei-Robison

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Drugs of abuse modulate the function and activity of the mesolimbic dopamine circuit. To identify novel mediators of drug-induced neuroadaptations in the ventral tegmental area (VTA), we performed RNA sequencing analysis on VTA samples from mice administered repeated saline, morphine, or cocaine injections. One gene that was similarly up-regulated by both drugs was serum- and glucocorticoid-inducible kinase 1 (SGK1). SGK1 activity, as measured by phosphorylation of its substrate N-myc downstream regulated gene (NDRG), was also increased robustly by chronic drug treatment. Increased NDRG phosphorylation was evident 1 but not 24 h after the last drug injection. SGK1 phosphorylation itself was similarly modulated. To determine the role of increased SGK1 activity on drug-related behaviors, we over-expressed constitutively active (CA) SGK1 in the VTA. SGK1-CA expression reduced locomotor sensitization elicited by repeated cocaine, but surprisingly had the opposite effect and promoted locomotor sensitization to morphine, without affecting the initial locomotor responses to either drug. SGK1-CA expression did not significantly affect morphine or cocaine conditioned place preference, although there was a trend toward increased conditioned place preference with both drugs. Further characterizing the role of this kinase in drug-induced changes in VTA may lead to improved understanding of neuroadaptations critical to drug dependence and addiction.

Original languageEnglish (US)
Pages (from-to)243-253
Number of pages11
JournalJournal of Neurochemistry
Volume132
Issue number2
DOIs
StatePublished - 2015

Fingerprint

Ventral Tegmental Area
Cocaine
Morphine
Glucocorticoids
Phosphotransferases
Pharmaceutical Preparations
Phosphorylation
Genes
Substance-Related Disorders
RNA Sequence Analysis
Drug therapy
Injections
serum-inducible kinase
Street Drugs
Dopamine
RNA
Networks (circuits)
Substrates

Keywords

  • cocaine
  • dopamine
  • locomotor activity
  • morphine
  • ventral tegmental area

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Morphine and cocaine increase serum- and glucocorticoid-inducible kinase 1 activity in the ventral tegmental area. / Heller, Elizabeth A.; Kaska, Sophia; Fallon, Barbara; Ferguson, Deveroux; Kennedy, Pamela J.; Neve, Rachael L.; Nestler, Eric J.; Mazei-Robison, Michelle S.

In: Journal of Neurochemistry, Vol. 132, No. 2, 2015, p. 243-253.

Research output: Contribution to journalArticle

Heller, EA, Kaska, S, Fallon, B, Ferguson, D, Kennedy, PJ, Neve, RL, Nestler, EJ & Mazei-Robison, MS 2015, 'Morphine and cocaine increase serum- and glucocorticoid-inducible kinase 1 activity in the ventral tegmental area', Journal of Neurochemistry, vol. 132, no. 2, pp. 243-253. https://doi.org/10.1111/jnc.12925
Heller, Elizabeth A. ; Kaska, Sophia ; Fallon, Barbara ; Ferguson, Deveroux ; Kennedy, Pamela J. ; Neve, Rachael L. ; Nestler, Eric J. ; Mazei-Robison, Michelle S. / Morphine and cocaine increase serum- and glucocorticoid-inducible kinase 1 activity in the ventral tegmental area. In: Journal of Neurochemistry. 2015 ; Vol. 132, No. 2. pp. 243-253.
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