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Status |
Public on May 18, 2023 |
Title |
EGR3 regulates opioid-related nociception and motivation in male rats |
Organism |
Rattus norvegicus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Chronic pain can be a debilitating condition, leading to profound changes in nearly every aspect of life. However, the reliance on opioids such as oxycodone for pain management is thought to initiate dependence and addiction liability. The neurobiological intersection at which opioids relieve pain and possibly transition to addiction is poorly understood. Using RNA sequencing pathway analysis in rats with complete Freund's adjuvant (CFA)-induced chronic inflammation, we found that the transcriptional signatures in the medial prefrontal cortex (mPFC; a brain region where pain and reward signals integrate) elicited by CFA in combination with oxycodone differed from those elicited by CFA or oxycodone alone. However, the expression of Egr3 was augmented in all animals receiving oxycodone. Furthermore, virus-mediated overexpression of EGR3 in the mPFC increased mechanical pain relief but not the affective aspect of pain in animals receiving oxycodone, whereas pharmacological inhibition of EGR3 via NFAT attenuated mechanical pain relief. Egr3 overexpression also increased the motivation to obtain oxycodone infusions in a progressive ratio test without altering the acquisition or maintenance of oxycodone self-administration. Taken together, these data suggest that EGR3 in the mPFC is at the intersection of nociceptive and addictive-like behaviors.
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Overall design |
The experiment is a 2x2 factorial design, with pain (CFA or saline) and drug (oxycodone or saline) as independent variables. Rats received injections of either CFA to induce chronic pain or saline as a control. Thereafter, they receive injections of oxycodone or saline (IP, daily, 7 days). Animals were euthanized at the end of the experiment and brains extracted. The mPFC was removed and RNA extracted for RNA-seq analysis.
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Contributor(s) |
Mitra S, Thomas SA, Martin JA, Williams J, Woodhouse K, Chandra R, Li JX, Lobo MK, Sim FJ, Dietz DM |
Citation(s) |
36098762 |
NIH grant(s) |
Grant ID |
Grant title |
Affiliation |
Name |
U01 DA051947 |
Heroin-Induced genomic regulation of Ventral Pallidum neuron subtypes |
UNIVERSITY AT BUFFALO, STATE UNIVERSITY OF NEW YORK |
DAVID M DIETZ |
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Submission date |
May 18, 2023 |
Last update date |
May 18, 2023 |
Contact name |
Fraser James Sim |
E-mail(s) |
[email protected]
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Phone |
7168292151
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Organization name |
University at Buffalo
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Department |
Pharmacology
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Street address |
3435 Main Street
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City |
Buffalo |
State/province |
NY |
ZIP/Postal code |
14216 |
Country |
USA |
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Platforms (1) |
GPL20084 |
Illumina NextSeq 500 (Rattus norvegicus) |
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Samples (36)
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Relations |
BioProject |
PRJNA973998 |
Supplementary file |
Size |
Download |
File type/resource |
GSE232804_counts.csv.gz |
725.6 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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