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          Institute: MPI für Psychiatrie     Collection: Publikationen MPI für Psychiatrie     Display Documents

ID: 4130.0, MPI für Psychiatrie / Publikationen MPI für Psychiatrie
Cocaine sensitization and reward are under the influence of circadian genes and rhythm
Authors:Abarca, C; Albrecht, U; Spanagel, R
Date of Publication (YYYY-MM-DD):2002-06-25
Title of Journal:Proceedings of the National Academy of Sciences of the United States of America
Journal Abbrev.:Proc. Natl. Acad. Sci. U. S. A.
Issue / Number:13
Start Page:9026
End Page:9030
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:Investigations using the fruit fly Drosophila melanogaster have shown that the circadian clock gene period (Per) can influence behavioral responses to cocaine. Here we show that the mouse homologues of the Drosophila Per gene, mPer1 and mPer2, modulate cocaine sensitization and reward, two phenomena extensively studied in humans and animals because of their importance for drug abuse. In response to an acute cocaine injection mPer1 and mPer2 mutant mice as well as wild-type mice exhibited an approximately 5-fold increase in activity compared with saline control levels, showing that there is no initial difference in sensitivity to acute cocaine administration in Per mutants. After repeated cocaine injections wild-type mice exhibited a sensitized behavioral response that was absent in mPer1 knockout mice. In contrast, mPer2 mutant mice exhibited a hypersensitized response to cocaine. Conditioned place preference experiments revealed similar behavioral reactions: mPer1 knockout mice showed a complete lack of cocaine reward whereas mPer2 mutants showed a strong cocaine-induced place preference. In another set of experiments, we tested C57/BL6J mice at different Zeitgeber times and found that cocaine- induced behavioral sensitization and place preference are under the control of the circadian clock. In conclusion, we demonstrate that processes involved in cocaine addiction depend on the circadian rhythm and are modulated in an opposing manner by mPer1 and mPer2 genes
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für Psychiatrie
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