期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 102, 期 26, 页码 9377-9381出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0503584102
关键词
circadian rhythms; dopamine; drug addiction; tyrosine hydroxylase
资金
- Howard Hughes Medical Institute Funding Source: Medline
- NIDA NIH HHS [K01 DA017750] Funding Source: Medline
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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