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Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9377-81. Epub 2005 Jun 20.

Regulation of dopaminergic transmission and cocaine reward by the Clock gene.

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Department of Psychiatry and Center for Basic Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9070, USA.


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.

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