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| Status |
Public on Aug 30, 2023 |
| Title |
Abstinence from Escalation of Cocaine Intake Changes the microRNA Landscape in the Cortico-Accumbal Pathway |
| Organism |
Rattus norvegicus |
| Experiment type |
Non-coding RNA profiling by high throughput sequencing
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| Summary |
Cocaine administration alters the microRNA (miRNA) landscape in the cortico-accumbal pathway. These changes in miRNA can play a major role in the posttranscriptional regulation of gene expression during withdrawal. This study aimed to investigate the changes in microRNA expression in the cortico-accumbal pathway during acute withdrawal and protracted abstinence following escalated cocaine intake. Small RNA sequencing (sRNA-seq) was used to profile miRNA
transcriptomic changes in the cortico-accumbal pathway [infralimbic- and prelimbic-prefrontal cortex (IL and PL) and nucleus accumbens (NAc)] of rats with extended access to cocaine self-administration followed by an 18-h withdrawal or a 4-week abstinence. An 18-h withdrawal led to differential expression (fold-change > 1.5 and p < 0.05) of 21 miRNAs in the IL, 18 miRNAs in the PL, and two miRNAs in the NAc. The mRNAs potentially targeted by these miRNAs were enriched in the following pathways: gap junctions, neurotrophin signaling, MAPK signaling, and cocaine addiction. Moreover, a 4-week abstinence led to differential expression (fold-change > 1.5 and p < 0.05) of 23 miRNAs in the IL, seven in the PL, and five miRNAs in the NAc. The mRNAs potentially targeted by these miRNAs were enriched in pathways including gap junctions, cocaine addiction, MAPK signaling,
glutamatergic synapse, morphine addiction, and amphetamine addiction. Additionally, the expression levels of several miRNAs differentially expressed in either the IL or the NAc were significantly correlated with addiction behaviors. Our findings highlight the impact of acute and protracted abstinence from escalated cocaine intake on miRNA expression in the cortico-accumbal pathway, a key circuit in addiction, and suggest developing novel biomarkers and therapeutic approaches to prevent relapse by targeting abstinence-associated miRNAs and their regulated mRNAs.
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| Overall design |
Compare miRNA transcriptome profiles among the three groups of rats (4-week abstinence vs. naïve; 16-hr withdrawal vs. naïve; and 4-week abstinence vs. 16-hr withdrawal)
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| Contributor(s) |
Huiping Z |
| Citation(s) |
37239038 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 AA025080 |
Brain microRNA-mRNA regulatory networks and alcohol use disorders |
BOSTON UNIVERSITY |
Huiping Zhang |
| R01 AA029758 |
Identifying Brain Epitranscriptomic Changes Associated with Alcohol Use Disorder |
BOSTON UNIVERSITY |
Huiping Zhang |
| U01 DA043799 |
Identification of Genetic Variants that Contribute to Compulsive Cocaine Intakein Rats |
THE REGENTS OF THE UNIV. OF CALIF., UNIV. OF CALIF., SAN DIEGO |
Olivier George |
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| Submission date |
Sep 03, 2022 |
| Last update date |
Aug 30, 2023 |
| Contact name |
Huiping Zhang |
| E-mail(s) |
[email protected]
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| Organization name |
Boston University
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| Street address |
72 East Concord Street
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02118 |
| Country |
USA |
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| Platforms (1) |
| GPL18694 |
Illumina HiSeq 2500 (Rattus norvegicus) |
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| Samples (36)
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| Relations |
| BioProject |
PRJNA876564 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE212651_Raw_gene_counts_matrix.txt.gz |
36.5 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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