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Gnao1 (G alphaO protein) is a likely genetic contributor to variation in physical dependence on opioids in mice.

Publication ,  Journal Article
Kest, B; Smith, SB; Schorscher-Petcu, A; Austin, J-S; Ritchie, J; Klein, G; Rossi, GC; Fortin, A; Mogil, JS
Published in: Neuroscience
September 15, 2009

Chronic exposure to opioids leads to physical dependence, which manifests as the symptoms of drug withdrawal. Interindividual differences in withdrawal symptom severity are well known, and at least partially due to genetic variation. To identify genes contributing to variation in withdrawal severity, we chronically treated 30 strains of the AcB/BcA recombinant congenic mouse strain set, including their A/J and C57BL/6J (B6) progenitors, with morphine for seven days and compared jumping frequencies--a sensitive and widely used index of withdrawal magnitude--during naloxone-precipitated withdrawal (NPW). Jumping frequencies of B6 mice were more than threefold greater than values obtained in A/J mice. Visual inspection of the genomic distribution of parental haplotypes in the AcB/BcA strains identified a putative quantitative trait locus (QTL) localized to chromosome 8 (90-117 Mb), and this QTL was confirmed in a B6AF2 intercross. The most salient candidate gene within this QTL, Gnao1 (guanine nucleotide binding protein, alpha(o); G alpha(o); 96.3 Mb), was tested for functional relevance using quantitative PCR and an antisense oligodeoxynucleotide strategy. The expression of Gnao1 in the locus coeruleus was found to be upregulated in morphine-dependent B6 but not A/J mice. Antisense knockdown of Gnao1 reduced NPW jumping in B6, but not A/J, mice rendered dependent on either morphine or heroin, largely rescuing the original strain difference. These data strongly implicate the G alpha(o) protein in the locus coeruleus as contributing to interindividual variability in physical dependence on opioids in mice.

Duke Scholars

Published In

Neuroscience

DOI

EISSN

1873-7544

Publication Date

September 15, 2009

Volume

162

Issue

4

Start / End Page

1255 / 1264

Location

United States

Related Subject Headings

  • Substance Withdrawal Syndrome
  • Species Specificity
  • Quantitative Trait Loci
  • Oligonucleotides, Antisense
  • Neurology & Neurosurgery
  • Naloxone
  • Morphine Dependence
  • Mice, Congenic
  • Mice
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
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Kest, B., Smith, S. B., Schorscher-Petcu, A., Austin, J.-S., Ritchie, J., Klein, G., … Mogil, J. S. (2009). Gnao1 (G alphaO protein) is a likely genetic contributor to variation in physical dependence on opioids in mice. Neuroscience, 162(4), 1255–1264. https://doi.org/10.1016/j.neuroscience.2009.05.027
Kest, B., S. B. Smith, A. Schorscher-Petcu, J. -. S. Austin, J. Ritchie, G. Klein, G. C. Rossi, A. Fortin, and J. S. Mogil. “Gnao1 (G alphaO protein) is a likely genetic contributor to variation in physical dependence on opioids in mice.Neuroscience 162, no. 4 (September 15, 2009): 1255–64. https://doi.org/10.1016/j.neuroscience.2009.05.027.
Kest B, Smith SB, Schorscher-Petcu A, Austin J-S, Ritchie J, Klein G, et al. Gnao1 (G alphaO protein) is a likely genetic contributor to variation in physical dependence on opioids in mice. Neuroscience. 2009 Sep 15;162(4):1255–64.
Kest, B., et al. “Gnao1 (G alphaO protein) is a likely genetic contributor to variation in physical dependence on opioids in mice.Neuroscience, vol. 162, no. 4, Sept. 2009, pp. 1255–64. Pubmed, doi:10.1016/j.neuroscience.2009.05.027.
Kest B, Smith SB, Schorscher-Petcu A, Austin J-S, Ritchie J, Klein G, Rossi GC, Fortin A, Mogil JS. Gnao1 (G alphaO protein) is a likely genetic contributor to variation in physical dependence on opioids in mice. Neuroscience. 2009 Sep 15;162(4):1255–1264.
Journal cover image

Published In

Neuroscience

DOI

EISSN

1873-7544

Publication Date

September 15, 2009

Volume

162

Issue

4

Start / End Page

1255 / 1264

Location

United States

Related Subject Headings

  • Substance Withdrawal Syndrome
  • Species Specificity
  • Quantitative Trait Loci
  • Oligonucleotides, Antisense
  • Neurology & Neurosurgery
  • Naloxone
  • Morphine Dependence
  • Mice, Congenic
  • Mice
  • Male