TY - JOUR
T1 - Gene profiling the response to repeated cocaine self-administration in dorsal striatum
T2 - A focus on circadian genes
AU - Lynch, Wendy J.
AU - Girgenti, Matthew J.
AU - Breslin, Florence J.
AU - Newton, Samuel S.
AU - Taylor, Jane R.
N1 - Funding Information:
The research described in the manuscript was supported by NIH and NIDA grants AR049469 (JRT and MRP), R01 DA11717 (JRT), R03 DA018978 (WJL), and by NINDS U24 grant NS051869-01 (SSN).
PY - 2008/6/5
Y1 - 2008/6/5
N2 - 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.
AB - 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.
KW - Dopamine
KW - Gene expression
KW - Glutamate
KW - Rat microarray
UR - http://www.scopus.com/inward/record.url?scp=44449148179&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2008.02.106
DO - 10.1016/j.brainres.2008.02.106
M3 - Article
C2 - 18452895
AN - SCOPUS:44449148179
SN - 0006-8993
VL - 1213
SP - 166
EP - 177
JO - Brain Research
JF - Brain Research
ER -