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

Research output: Contribution to journalArticlepeer-review

406 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


Dive into the research topics of 'Regulation of dopaminergic transmission and cocaine reward by the Clock gene'. Together they form a unique fingerprint.

Cite this