GeneSet Information

Tier III GS410093 • Gene expression in mouse nucleus accumbens (NAc) with expression pattern C cocaine + re-exposure (CC) vs baseline (S24)_pvalue

DESCRIPTION:

RNA-seq was performed on PFC, dorsal striatum (DStr), NAc, basolateral amygdala (BLA), ventral hippocampus (vHIP), and VTA, obtained from the following six groups of male C57BL/6J mice (Figure 1A): saline SA + 24 hr withdrawal (WD) (S24, n=5–8); cocaine SA + 24 hr WD (C24, n=5–8); saline SA + 30 d WD + saline re-exposure (SS, n=5–8); saline SA + 30 d WD + cocaine exposure (SC, n=5–8); cocaine SA + 30 d WD + saline exposure (CS, n=3–7); and cocaine SA + 30 d WD + cocaine re-exposure (CC, n=5–7). To focus on genes that were uniquely altered following context/drug re-exposure after WD, we compared all groups to the same baseline (S24). We focused on three patterns associated with drug use: first-ever exposure to cocaine (SC; Pattern A; Figure 2B), re-exposure to cocaine-paired context (CS, Pattern B, Figure 2C), and re-exposure to cocaine-paired context + cocaine (CC, Pattern C, Figure 2D). Each Pattern includes genes that were both differentially expressed from S24 (p<0.05; fold change>15%) and distinct from all other groups. The pattern C genes were significantly differentially expressed (see above) between the cocaine SA with cocaine re-exposure after 30 days and baseline (i.e. CC vs S4). Differential expression of the pattern C genes are presented for each group (C24 vs S24, SS vs S4, SC vs S4, CS vs S4, and CC vs S4).

LABEL:

Gene expression mouse NAc pattern C CC vs S24_pvalue

SCORE TYPE:

P-Value

THRESHOLD:

<= 0.05

GENES IN THRESHOLD:

372

DATE ADDED:

2025-01-09

DATE UPDATED:

2025-06-19

SPECIES:

AUTHORS:

Deena M Walker, Hannah M Cates, Yong-Hwee E Loh, Immanuel Purushothaman, Aarthi Ramakrishnan, Kelly M Cahill, Casey K Lardner, Arthur Godino, Hope G Kronman, Jacqui Rabkin, Zachary S Lorsch, Philipp Mews, Marie A Doyle, Jian Feng, Benoit Labonté, Ja Wook Koo, Rosemary C Bagot, Ryan W Logan, Marianne L Seney, Erin S Calipari, Li Shen, Eric J Nestler

TITLE:

Cocaine Self-administration Alters Transcriptome-wide Responses in the Brain's Reward Circuitry.

JOURNAL:

Biological psychiatry Dec 2018, Vol 84, pp. 867-880

ABSTRACT:

Background: Global changes in gene expression underlying circuit and behavioral dysregulation associated with cocaine addiction remain incompletely understood. Here, we show how a history of cocaine self-administration (SA) reprograms transcriptome-wide responses throughout the brain's reward circuitry at baseline and in response to context and/or cocaine re-exposure after prolonged withdrawal (WD). Methods: We assigned male mice to one of six groups: saline/cocaine SA + 24-hour WD or saline/cocaine SA + 30-day WD + an acute saline/cocaine challenge within the previous drug-paired context. RNA sequencing was conducted on six interconnected brain reward regions. Using pattern analysis of gene expression and factor analysis of behavior, we identified genes that are strongly associated with addiction-related behaviors and uniquely altered by a history of cocaine SA. We then identified potential upstream regulators of these genes. Results: We focused on three patterns of gene expression that reflect responses to 1) acute cocaine, 2) context re-exposure, and 3) drug + context re-exposure. These patterns revealed region-specific regulation of gene expression. Further analysis revealed that each of these gene expression patterns correlated with an addiction index-a composite score of several addiction-like behaviors during cocaine SA-in a region-specific manner. Cyclic adenosine monophosphate response element binding protein and nuclear receptor families were identified as key upstream regulators of genes associated with such behaviors. Conclusions: This comprehensive picture of transcriptome-wide regulation in the brain's reward circuitry by cocaine SA and prolonged WD provides new insight into the molecular basis of cocaine addiction, which will guide future studies of the key molecular pathways involved. PUBMED: 29861096
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Annotation Information

No sequence read archive data associated with this GeneSet.


Social Control, Formal (D012926)
Gene Expression Regulation (D005786)
Behavior (D001519)
Carrier Proteins (D002352)
Adenosine (D000241)
Adenosine Monophosphate (D000249)
Gene Expression (D015870)
Proteins (D011506)
Amygdala (D000679)
Pharmaceutical Preparations (D004364)
Cocaine-Related Disorders (D019970)
Receptors, Cytoplasmic and Nuclear (D018160)
Response Elements (D020218)
Cocaine (D003042)
Sequence Analysis, RNA (D017423)
Factor Analysis, Statistical (D005163)
Genes, vif (D016341)
Hippocampus (D006624)
dorsal striatum (MA:0002971)
hippocampus (MA:0000191)
addiction (MP:0002555)
biological regulation (GO:0065007)
nascent polypeptide-associated complex (GO:0005854)
gene expression (GO:0010467)
regulation of gene expression (GO:0010468)
Transcriptomics (EDAM_topic:0203)
Pathways, networks and models (EDAM_topic:0602)
N-acetyl-L-cysteine (CHEBI:28939)
(Z)-N-cyclopropyl-11-methyldodec-2-enamide (CHEBI:87143)
adenosine (CHEBI:16335)
maleate(2-) (CHEBI:30780)
cocaine(1+) (CHEBI:60056)
protein polypeptide chain (CHEBI:16541)
ribonucleic acid (CHEBI:33697)
perfluorinated compound (CHEBI:134091)
RNA-seq evidence (ECO:0000295)
obsolete_corpus striatum (EFO:0000381)
transcription profiling by high throughput sequencing (EFO:0002770)
cocaine dependence (EFO:0002610)
transcriptome (EFO:0004421)
RNA-seq assay (MMO:0000659)
archicortex (UBERON:0002961)
Ammon's horn (UBERON:0001954)
hippocampal formation (UBERON:0002421)
male organism (UBERON:0003101)
ventral tegmental area (UBERON:0002691)
caudate-putamen (UBERON:0005383)
dorsal striatum (UBERON:0005382)
adult cerebral ganglion (UBERON:6110636)
basolateral amygdaloid nuclear complex (UBERON:0006107)

Gene List • 372 Genes

Genes in threshold: 372

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