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

被引：0

作者：

Freddyson J. Martínez-Rivera ^{[1
]}

Leanne M. Holt ^{[2
]}

Angélica Minier-Toribio ^{[1
]}

Molly Estill ^{[1
]}

Szu-Ying Yeh ^{[1
]}

Solange Tofani ^{[1
]}

Rita Futamura ^{[1
]}

Caleb J. Browne ^{[1
]}

Philipp Mews ^{[1
]}

Li Shen ^{[1
]}

Eric J. Nestler ^{[1
]}

机构：

[1] Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, NY

[2] Department of Neuroscience, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL

来源：

Nature Communications | / 16卷 / 1期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/s41467-025-58151-4

中图分类号：

学科分类号：

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. © The Author(s) 2025.

引用

共 93 条

[31] Rymut H.E., Et al., Prefrontal Cortex Response to Prenatal Insult and Postnatal Opioid Exposure, Genes (Basel), 13, (2022)
[32] Icick R., Et al., Genetic overlap between mood instability and alcohol-related phenotypes suggests shared biological underpinnings, Neuropsychopharmacology, 47, pp. 1883-1891, (2022)
[33] Berhow M.T., Hiroi N., Kobierski L.A., Hyman S.E., Nestler E.J., Influence of cocaine on the JAK-STAT pathway in the mesolimbic dopamine system, J. Neurosci, 16, pp. 8019-8026, (1996)
[34] Martinez-Sanchis S., Aragon C.M.G., Salvador A., Cocaine-induced locomotor activity is enhanced by exogenous testosterone, Physiol. Behav, 76, pp. 605-609, (2002)
[35] Menendez-Delmestre R., Segarra A.C., Testosterone is essential for cocaine sensitization in male rats, Physiol. Behav, 102, pp. 96-104, (2011)
[36] Dash S., Et al., Cocaine-regulated microRNA miR-124 controls poly (ADP-ribose) polymerase-1 expression in neuronal cells, Sci. Rep, 10, (2020)
[37] Shaham Y., Shalev U., Lu L., De Wit H., Stewart J., The reinstatement model of drug relapse: history, methodology and major findings, Psychopharmacology, 168, pp. 3-20, (2003)
[38] Kalivas P.W., Peters J., Knackstedt L., Animal models and brain circuits in drug addiction, Mol. Inter, 6, pp. 339-344, (2006)
[39] Maren S., Phan K.L., Liberzon I., The contextual brain: implications for fear conditioning, extinction and psychopathology, Nat. Rev. Neurosci, 14, pp. 417-428, (2013)
[40] Hennings A.C., McClay M., Lewis-Peacock J.A., Dunsmoor J.E., Contextual reinstatement promotes extinction generalization in healthy adults but not PTSD, Neuropsychologia, 147, (2020)

← 1 2 3 4 5 6 7 8 9 10 →