Transcriptional characterization of cocaine withdrawal versus extinction within nucleus accumbens in male rats

Freddyson J. Martínez-Rivera (), Leanne M. Holt (), Angélica Minier-Toribio, Molly Estill, Szu-Ying Yeh, Solange Tofani, Rita Futamura, Caleb J. Browne, Philipp Mews, Li Shen and Eric J. Nestler ()
Additional contact information
Freddyson J. Martínez-Rivera: Icahn School of Medicine at Mount Sinai
Leanne M. Holt: Icahn School of Medicine at Mount Sinai
Angélica Minier-Toribio: Icahn School of Medicine at Mount Sinai
Molly Estill: Icahn School of Medicine at Mount Sinai
Szu-Ying Yeh: Icahn School of Medicine at Mount Sinai
Solange Tofani: Icahn School of Medicine at Mount Sinai
Rita Futamura: Icahn School of Medicine at Mount Sinai
Caleb J. Browne: Icahn School of Medicine at Mount Sinai
Philipp Mews: Icahn School of Medicine at Mount Sinai
Li Shen: Icahn School of Medicine at Mount Sinai
Eric J. Nestler: Icahn School of Medicine at Mount Sinai

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Neurobiological alterations seen in addiction amplify during abstinence and compromise relapse prevention. Cocaine use disorder (CUD) exemplifies this phenomenon in which reward regions such as nucleus accumbens (NAc) undergo withdrawal-associated modifications. While genome-wide transcriptional changes in NAc are linked to specific addiction phases, these have not been examined in a context- and NAc-subregion-specific manner during withdrawal vs. extinction. We used cocaine self-administration in male rats combined with RNA-sequencing of NAc-core and -shell to transcriptionally profile withdrawal in the home-cage, in the previous drug context, or after extinction. As expected, home-cage withdrawal maintained seeking, whereas extinction reduced it. By contrast, withdrawal involving the drug context only increased seeking. Bioinformatic analyses revealed specific gene expression patterns and networks associated with these states. Comparing NAc datasets of CUD patients highlighted conserved transcriptomic signatures with rats experiencing withdrawal in the drug context. Together, this work reveals fundamental mechanisms that can be targeted to attenuate relapse.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-58151-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58151-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-58151-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().