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| Status |
Public on May 06, 2021 |
| Title |
Opioid withdrawal produces sex-specific effects on fentanyl-vs.-food choice and mesolimbic transcription |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background: Opioid withdrawal is a key driver of opioid addiction and an obstacle to recovery. However, withdrawal effects on opioid reinforcement and mesolimbic neuroadaptation are understudied and the role of sex is largely unknown. Methods: Male (n=13) and female (n=12) rats responded under a fentanyl-vs.-food “choice” procedure during daily 2h sessions. In addition to the daily choice sessions, rats were provided extended access to fentanyl during 12h self-administration sessions. After two weeks of this selfadministration regimen, the nucleus accumbens (NAc) and ventral tegmental area (VTA) of a subset of rats were subjected to RNA sequencing. In the remaining rats, a third week of this self-administration regimen was conducted, during which methadone effects on fentanyl-vs.-food choice were determined. Results: Prior to opioid dependence, male and female rats similarly allocated responding between fentanyl and food. Abstinence from extended fentanyl access elicited similar increases in somatic withdrawal signs in both sexes. Despite similar withdrawal signs and extended access fentanyl intake, opioid withdrawal was accompanied by a maladaptive increase in fentanyl choice in males, but not females. Behavioral sex differences corresponded with a greater number of differentially expressed genes in the NAc and VTA of opioidwithdrawn females relative to males. Methadone blocked withdrawal-associated increases in fentanyl choice in males, but failed to further decrease fentanyl choice in females. Conclusions: These results provide foundational evidence of sex-specific neuroadaptations to opioid withdrawal, which may be relevant to the female-specific resilience to withdrawal-associated increases in opioid choice and aid in the identification of novel therapeutic targets.
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| Overall design |
Bulk RNA sequencing from microdissected rat nucleus accumbens and ventral tegmental area brain areas, drug treated group DEGs generated relative to saline treated controls.
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| Contributor(s) |
Hamilton P |
| Citation(s) |
34458885 |
| Submission date |
May 05, 2021 |
| Last update date |
Oct 19, 2023 |
| Contact name |
Peter Hamilton |
| Organization name |
Virginia Commonwealth University
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| Department |
Anatomy and Neurobiology
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| Street address |
1217 E Marshall St
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| City |
Richmond |
| State/province |
VA |
| ZIP/Postal code |
23298 |
| Country |
USA |
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| Platforms (1) |
| GPL18694 |
Illumina HiSeq 2500 (Rattus norvegicus) |
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| Samples (24)
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| GSM5283509 |
NAc, Male, Fentanyl N7---NAc |
| GSM5283510 |
NAc, Female, Fentanyl L1---NAc |
| GSM5283511 |
NAc, Female, Fentanyl L2---NAc |
| GSM5283512 |
NAc, Female, Fentanyl L7---NAc |
| GSM5283513 |
NAc, Female, Fentanyl L8---NAc |
| GSM5283514 |
NAc, Male, Saline SM1---NAc |
| GSM5283515 |
NAc, Male, Saline SM3---NAc |
| GSM5283516 |
NAc, Male, Saline SM4---NAc |
| GSM5283517 |
NAc, Female, Saline SF1---NAc |
| GSM5283518 |
NAc, Female, Saline SF2---NAc |
| GSM5283519 |
NAc, Female, Saline SF4---NAc |
| GSM5283520 |
VTA, Male, Fentanyl N1---VTA |
| GSM5283521 |
VTA, Male, Fentanyl N2---VTA |
| GSM5283522 |
VTA, Male, Fentanyl N3---VTA |
| GSM5283523 |
VTA, Female, Fentanyl L1---VTA |
| GSM5283524 |
VTA, Female, Fentanyl L2---VTA |
| GSM5283525 |
VTA, Female, Fentanyl L7---VTA |
| GSM5283526 |
VTA, Male, Saline SM1---VTA |
| GSM5283527 |
VTA, Male, Saline SM3---VTA |
| GSM5283528 |
VTA, Female, Saline SF1---VTA |
| GSM5283529 |
VTA, Female, Saline SF2---VTA |
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| Relations |
| BioProject |
PRJNA727608 |
| SRA |
SRP318640 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE173959_RAW.tar |
51.8 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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