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.
Pubmed ID: 15967985 RIS Download
Mesh terms: Animals | Blotting, Western | Brain | CLOCK Proteins | Circadian Rhythm | Cocaine | Dopamine | Dose-Response Relationship, Drug | Electrophysiology | Homozygote | Immunohistochemistry | Male | Mice | Mice, Transgenic | Models, Neurological | Mutation | Neurons | Oligonucleotide Array Sequence Analysis | Phenotype | Phosphorylation | Point Mutation | Reward | Substance-Related Disorders | Time Factors | Trans-Activators | Tyrosine 3-Monooxygenase | Ventral Tegmental Area
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