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

被引：0

作者：

Martinez-Rivera, Freddyson J. ^{[1
,2
,3
]}

Holt, Leanne M. ^{[1
,2
]}

Minier-Toribio, Angelica ^{[1
,2
]}

Estill, Molly ^{[1
,2
]}

Yeh, Szu-Ying ^{[1
,2
]}

Tofani, Solange ^{[1
,2
]}

Futamura, Rita ^{[1
,2
]}

Browne, Caleb J. ^{[1
,2
]}

Mews, Philipp ^{[1
,2
]}

Shen, Li ^{[1
,2
]}

Nestler, Eric J. ^{[1
,2
]}

机构：

[1] Icahn Sch Med Mt Sinai, Nash Family Dept Neurosci, New York, NY 10029 USA

[2] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA

[3] Univ Florida, Coll Med, McKnight Brain Inst, Dept Neurosci, Gainesville, FL 32611 USA

来源：

NATURE COMMUNICATIONS | 2025年 / 16卷 / 01期

关键词：

GENE-EXPRESSION; ANIMAL-MODELS; BRAIN; DRUG; DOPAMINE; RELAPSE; SEEKING; FEAR; REINSTATEMENT; MECHANISMS;

D O I：

10.1038/s41467-025-58151-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：16

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