title: Regulation of dopaminergic transmission and cocaine reward by the Clock gene.
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.
authors.affiliation: Department of Psychiatry and Center for Basic Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9070, USA.
authors.forename: Colleen A
authors.initials: CA
authors.lastname: McClung
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Sidiropoulou
authors.forename: Martha
authors.initials: M
authors.lastname: Vitaterna
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Takahashi
authors.forename: Francis J
authors.initials: FJ
authors.lastname: White
authors.forename: Donald C
authors.initials: DC
authors.lastname: Cooper
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Nestler
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D056926:CLOCK Proteins; D002940:Circadian Rhythm; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006720:Homozygote; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008959:Models, Neurological; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D010766:Phosphorylation; D017354:Point Mutation; D012201:Reward; D019966:Substance-Related Disorders; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000378:metabolism / Q000502:physiology*
chemical_list: D015534:Trans-Activators; D014446:Tyrosine 3-Monooxygenase; D056926:CLOCK Proteins; C538944:Clock protein, mouse; D003042:Cocaine; D004298:Dopamine