|
| Status |
Public on Jun 07, 2024 |
| Title |
Single-nuclei characterization of oxycodone's effects on dorsal peduncular nucleus |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
In addition to their intrinsic rewarding properties. opioids can also evoke aversive reactions that protect against misuse. Cellular mechanisms that govern the interplay between opioid reward and aversion are poorly understood. We used whole-brain activity mapping to show that neurons in the dorsal peduncular nucleus (DPn) are highly responsive to the opioid oxycodone. Connectomic profiling revealed that DPn neurons innervate the parabrachial nucleus (PBn). Spatial and single-nuclei transcriptomics resolved a unique population of PBn-projecting pyramidal neurons restricted to the DPn that express μ-opioid receptors (μORs). Disrupting μOR signaling in these neurons switched oxycodone from rewarding to aversive and exacerbated the severity of opioid withdrawal. These findings identify DPn neurons as key substrates for the abuse liability of opioids.
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| |
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| Overall design |
2 saline-injected (IP) samples, 2 oxycodone-injected (5mg/kg) samples
|
| Web link |
https://www.science.org/doi/10.1126/science.adn0886
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| |
|
| Contributor(s) |
Smith AC, Kenny PJ, Beaumont K, Sebra RP |
| Citation(s) |
38843332 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R00 DA048119 |
Discovery of novel pharmacotherapeutic targets for opioid addiction |
MEDICAL UNIVERSITY OF SOUTH CAROLINA |
Alexander Wanless Smith |
| U01 DA053629 |
Single cell brain transcriptome changes during chronic HIV infection and opiate use in conventional mice |
MOUNT SINAI SCHOOL OF MEDICINE |
Paul J. Kenny |
| P01 DA047233 |
Transcriptional Mechanisms of Drug Addiction |
MOUNT SINAI SCHOOL OF MEDICINE |
Eric J. Nestler |
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| |
| Submission date |
Mar 01, 2024 |
| Last update date |
Oct 18, 2024 |
| Contact name |
Alexander CW Smith |
| E-mail(s) |
[email protected]
|
| Phone |
843-792-8872
|
| Organization name |
Medical University of South Carolina
|
| Department |
Neuroscience
|
| Street address |
173 Ashley Ave, BS403
|
| City |
Charleston |
| State/province |
SC |
| ZIP/Postal code |
29425 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (4)
|
|
| Relations |
| BioProject |
PRJNA1082687 |
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