GeneSet Information

Tier III GS400188 • Differentially expressed genes in the central amygdala of rats on day 2 of methamphetamine withdrawal (RNA-seq)


Differentially expressed geens in the central amygdala (CeA) of male Sprague-Dawley rats (300-350 g prior to surgery, 325-375 g at start of self-administration) on day 2 following methamphetamine withdrawal. Gene Expression was evaluated via RNA-seq. Data taken from Supplementary Table S2. Values presented are adjusted p-values. Data available from GEO with accession number GSE111243."


CeA Day 2 Meth vs Saline









Hannah M Cates, Xuan Li, Immanuel Purushothaman, Pamela J Kennedy, Li Shen, Yavin Shaham, Eric J Nestler


Genome-wide transcriptional profiling of central amygdala and orbitofrontal cortex during incubation of methamphetamine craving.


Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 11 2018, Vol 43, pp. 2426-2434


Methamphetamine (Meth) seeking progressively increases after withdrawal (incubation of Meth craving), but the transcriptional mechanisms that contribute to this incubation are unknown. Here we used RNA-sequencing to analyze transcriptional profiles associated with incubation of Meth craving in central amygdala (CeA) and orbitofrontal cortex (OFC), two brain areas previously implicated in relapse to drug seeking. We trained rats to self-administer either saline (control condition) or Meth (10 days; 9 h/day, 0.1 mg/kg/infusion). Next, we collected brain tissue from CeA and OFC on withdrawal day 2 (when Meth seeking is low and non-incubated) and on day 35 (when Meth seeking is high and incubated), for subsequent RNA-sequencing. In CeA, we identified 10-fold more differentially expressed genes (DEGs) on withdrawal day 35 than day 2. These genes were enriched for several biological processes, including protein ubiquitination and histone methylation. In OFC, we identified much fewer expression changes than in CeA, with more DEGs on withdrawal day 2 than on day 35. There was a significant overlap between upregulated genes on withdrawal day 2 and downregulated genes on withdrawal day 35 in OFC. Our analyses highlight the CeA as a key region of transcriptional regulation associated with incubation of Meth seeking. In contrast, transcriptional regulation in OFC may contribute to Meth seeking during early withdrawal. Overall, these findings provide a unique resource of gene expression data for future studies examining transcriptional mechanisms in CeA that mediate Meth seeking after prolonged withdrawal. PUBMED: 30072726
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Annotation Information

withdrawal response to addictive substance trait (VT:0010722)
response to methamphetamine trait (VT:0010719)
response to addictive substance trait (VT:0010488)
response to xenobiotic stimulus trait (VT:0010487)
organism trait (VT:0010454)
central amygdaloid nucleus (UBERON:0002883)

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