Overexpression of dopamine D2 receptors reduces alcohol self-administration

Panayotis K. Thanos, Nora D. Volkow, Paul Freimuth, Hiroyuki Umegaki, Hiroyuki Ikari, George Roth, Donald K. Ingram, Robert Hitzemann

Research output: Contribution to journalArticlepeer-review

253 Scopus citations


The mechanism(s) underlying predisposition to alcohol abuse are poorly understood but may involve brain dopamine system(s). Here we used an adenoviral vector to deliver the dopamine D2 receptor (DRD2) gene into the nucleus accumbens of rats, previously trained to self-administer alcohol, and to assess if DRD2 levels regulated alcohol preference and intake. We show that increases in DRD2 (52%) were associated with marked reductions in alcohol preference (43%), and alcohol intake (64%) of ethanol preferring rats, which recovered as the DRD2, returned to baseline levels. In addition, this DRD2 overexpression similarly produced significant reductions in ethanol non-preferring rats, in both alcohol preference (16%) and alcohol intake (75%). This is the first evidence that overexpression of DRD2 reduces alcohol intake and suggests that high levels of DRD2 may be protective against alcohol abuse.

Original languageEnglish (US)
Pages (from-to)1094-1103
Number of pages10
JournalJournal of neurochemistry
Issue number5
StatePublished - 2001


  • Adenovirus
  • Alcoholism
  • Animal model
  • Drinking preference
  • Gene therapy
  • Nucleus accumbens

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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