My lab focuses on the influence of circadian rhythms and genes that make up the molecular clock in psychiatric disorders. It has been speculated for some time that circadian rhythms may be critically involved in both the manifestation and treatment of psychiatric disorders, particularly disorders with repetitive patterns such as seasonal affective disorder (SAD), major depression,schizophrenia,and bipolar disorder. Indeed, nearly all pyschiatric conditions are associated with altered patterns of sleep and abnormal circadian rhythms. As well, depression symptoms occur more often in the morning and in areas of the world that recieve little sunlight for long periods of time. Furthermore, in human populations, polymorphisms or mutations in genes involved in regulating circadian rhythms including CLOCK, the Period genes, and NPAS2, have been linked to several psychiatric diseases. Circadian genes are also involved in regulating the rewarding and addictive properties of drugs like cocaine, morphine and alcohol. The genes that make up the molecular clock exert many of their effects on mood and motivational state through their regulation of circadian rhythms and sleep. In addition, we have found that these genes have novel functions outside of the central circadian pacemaker in regions of the brain that are important for mental health. Our goal is to combine behavioral and molecular biology to characterize the role of these genes in the manifestation and the treatment of psychiatric disorders.
RESEARCH INTERESTS
Mood disorders
Drug addiction
circadian rhythms
RECENT PUBLICATIONS
McClung, C.A., Nestler, E.J., Zachariou, V., "Regulation of gene expression by chronic morphine and morphine withdrawal in the locus ceruleus and ventral tegmental area" Journal of Neuroscience, 25(25):6005-6015, 2005
Wallace DL, Han MH, Graham DL, Green TA, Vialou V, Iniguez SD, Cao JL, Kirk A, Chakravarty S, Kumar A, Krishnan V, Neve RL, Cooper DC, Bolanos CA, Barrot M, McClung CA, Nestler EJ, "CREB regulation of nucleus accumbens excitability mediates social isolation-induced behavioral deficits" Nature Neuroscience, 12:200-209, February 2009
McClung, C.A., "The molecular mechanisms of morphine addiction" Reviews in the Neurosciences, in press
Berton, O., McClung, C.A., Dileone R.J., Russo, S., Graham, D., Renthal, W., Tsankova, N., Bolanos, C.A., Rios, M., Self, D.W., Nestler, E.J., "Essential role of BDNF in dopaminergic reward regions in social defeat stress" Science, 311:864-686, 2006
McClung, C.A., "Circadian genes, rhythms, and the biology of mood disorders" Pharmacology and Therapeutics, 114:222-232, 2007
SIGNIFICANT PUBLICATIONS
McClung, C.A., Sidiropoulou, K., Vitaterna, M., Takahashi, J.S., White, F.J., Cooper, D.C., Nestler, E.J., "Regulation of dopaminergic transmission and cocaine reward by the Clock gene" Proc. Natl. Acad Sci. USA, 102(26):9377-9381, 2005
McClung, C.A. and Nestler, E.J., "Regulation of gene expression and cocaine reward by CREB and DeltaFosB" Nature Neuroscience, 6(11):1208-1215, 2003
McClung, C.A. and Hirsh, J., "Stereotypic behavioral responses to cocaine and the development of sensitization in Drosophila melanogaster" Current Biology, 8:109-112, 1998
Roybal, Kole; Theobold, David; Graham, Ami; DiNieri, Jennifer A.; Russo, Scott J; Krishnan, Vaishnav; Chakravarty, Sumana; Peevey, Joseph; Oehrlein, Nathan; Birnbaum, Shari; Vitaterna, Martha H.; Orsulak, Paul; Takahashi, Joseph S.; Nestler, Eric J.; Carlezon, William A. Jr.; and McClung, Colleen A., "Mania-like behavior induced by disruption of CLOCK" Proc Natl Acad Sci USA, 104(15):6406-6411, 2007
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