Regulation of dopaminergic transmission and cocaine reward by the Clock gene

Colleen A. McClung, Kyriaki Sidiropoulou, Martha Vitaterna, Joseph S. Takahashi, Francis J. White, Donald C. Cooper, Eric J. Nestler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

427 Scopus citations


Although there are clear interactions between circadian rhythms and drug addiction, mechanisms for such interactions remain unknown. Here we establish a role for the Clock gene in regulating the brain's reward circuit. Mice lacking a functional Clock gene display an increase in cocaine reward and in the excitability of dopamine neurons in the midbrain ventral tegmental area, a key brain reward region. These phenotypes are associated with increased expression and phosphorylation of tyrosine hydroxylase (the rate-limiting enzyme in dopamine synthesis), as well as changes in several genes known to regulate dopamine activity in the ventral tegmental area. These findings demonstrate the involvement of a circadian-associated gene, Clock, in regulating dopamine function and cocaine reward.

Original languageEnglish (US)
Pages (from-to)9377-9381
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number26
StatePublished - Jun 28 2005


  • Circadian rhythms
  • Dopamine
  • Drug addiction
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • General


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