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Regulation of Dopaminergic Neurotransmission and Cocaine Reward by the Clock Gene (McClung et al, 20

Regulation of Dopaminergic Neurotransmission and Cocaine Reward by the Clock Gene (McClung et al, 20

  1. Jatelka
    Proceedings of the National Academy of Sciences of the United States of America June 28, 2005 vol. 102 no. 26 9377–9381

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

    Abstract
    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.