Gene profiling the response to repeated cocaine self-administration in dorsal striatum: A focus on circadian genes

Wendy J. Lynch, Matthew J. Girgenti, Florence J. Breslin, Samuel S. Newton, Jane R. Taylor

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Alterations in gene expression in the dorsal striatum caused by chronic cocaine exposure have been implicated in the long-term behavioral changes associated with cocaine addiction. To gain further insight into the molecular alterations that occur as a result of cocaine self-administration, we conducted a microarray analysis of gene expression followed by bioinformatic gene network analysis that allowed us to identify adaptations at the level of gene expression as well as into interconnected networks. Changes in gene expression were examined in the dorsal striatum of rats 1 day after they had self-administered cocaine for 7 days under a 24-h access, discrete trial paradigm (averaging 98 mg/kg/day). Here we report the regulation of the circadian genes Clock, Bmal1, Cryptochrome1, Period2, as well as several genes that are regulated by/associated with the circadian system (i.e., early growth response 1, dynorphin). We also observed regulation of other relevant genes (i.e., Nur77, beta catenin). These changes were then linked to curated pathways and formulated networks which identified circadian rhythm processes as affected by cocaine self-administration. These data strongly suggest involvement of circadian-associated genes in the brain's response to cocaine and may contribute to an understanding of addictive behavior including disruptions in sleep and circadian rhythmicity.

Original languageEnglish (US)
Pages (from-to)166-177
Number of pages12
JournalBrain Research
Volume1213
DOIs
StatePublished - Jun 5 2008

Fingerprint

Self Administration
Cocaine
Gene Expression
Genes
Addictive Behavior
Dynorphins
Cocaine-Related Disorders
Circadian Clocks
Gene Regulatory Networks
beta Catenin
Periodicity
Microarray Analysis
Circadian Rhythm
Computational Biology
Sleep
Brain
Growth

Keywords

  • Dopamine
  • Gene expression
  • Glutamate
  • Rat microarray

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Gene profiling the response to repeated cocaine self-administration in dorsal striatum : A focus on circadian genes. / Lynch, Wendy J.; Girgenti, Matthew J.; Breslin, Florence J.; Newton, Samuel S.; Taylor, Jane R.

In: Brain Research, Vol. 1213, 05.06.2008, p. 166-177.

Research output: Contribution to journalArticle

Lynch, Wendy J. ; Girgenti, Matthew J. ; Breslin, Florence J. ; Newton, Samuel S. ; Taylor, Jane R. / Gene profiling the response to repeated cocaine self-administration in dorsal striatum : A focus on circadian genes. In: Brain Research. 2008 ; Vol. 1213. pp. 166-177.
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