Nucleus accumbens AGS3 expression drives ethanol seeking through Gβγ

M. Scott Bowers, F. Woodward Hopf, Jonathan K. Chou, Anitra M. Guillory, Shao Ju Chang, Patricia H. Janak, Antonello Bonci, Ivan Diamond

Research output: Contribution to journalArticlepeer-review

Abstract

Approximately 90% of alcoholics relapse within 4 years, in part because of an enhanced motivation to seek alcohol (EtOH). A novel G protein modulator (Gpsm1/AGS3) was up-regulated in the rat nucleus accumbens core (NAcore) but not in other limbic nuclei during abstinence from operant EtOH self-administration. Furthermore, NAcore AGS3 knockdown reduced EtOH seeking to preabstinence levels in a novel rat model of compulsive, human EtOH seeking. AGS3 can both inhibit G protein Giα-mediated signaling and stimulate Gβγ-mediated signaling. Accordingly, sequestration of Gβγ, but not Giα knockdown, significantly reduced EtOH seeking to pre-abstinence levels. Thus, AGS3 and Gβγ are hypothesized to gate the uncontrolled motivation to seek EtOH during abstinence. AGS3 up-regulation during abstinence may be a key determinant of the transition from social consumption to compulsion-like seeking during relapse.

Original languageEnglish (US)
Pages (from-to)12533-12538
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number34
DOIs
StatePublished - Aug 26 2008
Externally publishedYes

Keywords

  • Alcohol deprivation effect
  • G protein
  • Giα
  • Reinstatement
  • Self-administration

ASJC Scopus subject areas

  • General

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