Gene profiling the response to repeated cocaine self-administration in dorsal striatum: a focus on circadian genes.
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.
Lynch
Wendy J
WJ
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, USA. wlynch@virginia.edu
Girgenti
Matthew J
MJ
Breslin
Florence J
FJ
Newton
Samuel S
SS
Taylor
Jane R
JR
D000818:Animals; D016739:Behavior, Addictive / Q000139:chemically induced / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics*; D003042:Cocaine / Q000008:administration & dosage*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling / Q000379:methods; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013997:Time Factors
D018765:Dopamine Uptake Inhibitors; D003042:Cocaine