Gene expression profile from the striatum of amphetamine-treated rats: a cDNA array and in situ hybridization histochemical study.
Changes in gene/protein expression markedly outlast the transient changes in behavior evoked by a single dose of a psychostimulant. These changes in gene expression are thought to underlie and/or trigger enduring changes in neuroplasticity that lead to drug addiction. We used cDNA arrays to gain a more complete picture of changes in striatal gene expression 1 and 3 h after an acute injection of amphetamine. Consistent, reliable gene expression changes were detected when criteria of at least a 1.5-fold difference and three replicate hybridizations using independent samples were performed. Using these criteria, the mRNA for three immediate early genes (IEGs), coding for activity-regulated cytoskeletal-associated protein (Arc), nerve growth factor-induced protein A (NGFI-A; early growth response protein 1) and nerve growth factor-induced protein B (NGFI-B), were upregulated 1 and 3 h after amphetamine as previously described. Novel genes, RL/IF-1 (coding for I kappa B alpha chain) and serum/glucocorticoid-regulated serine/threonine protein kinase (SGK) also were increased throughout the striatum, at 1 but not 3 h. Conversely, amphetamine increased the mRNA coding for the secretogranin II precursor (chromogranin C) only at the 3 h time point when a specific decrease in regulator of G-protein signaling 4 (RGS4) mRNA was also observed. Gene changes and unique patterns of expression were verified by in situ hybridization, providing valuable information about changes in gene expression in response to acute amphetamine.
Gonzalez-Nicolini
Valeria
V
Department of Physiology and Neuroscience, Medical University of South Carolina, 173 Ashley Avenue, BSB 403, Charleston, SC 29425, USA.
McGinty
Jacqueline F
JF
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics*; D020869:Gene Expression Profiling; D017781:Genes, Immediate-Early; D006651:Histocytochemistry; D017874:Immediate-Early Proteins / Q000235:genetics; D017403:In Situ Hybridization; D007700:Kinetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics*; D051381:Rats; D013997:Time Factors
D018076:DNA, Complementary; D017874:Immediate-Early Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000661:Amphetamine