ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
SIRT1-FOXO3a regulate cocaine actions in the nucleus accumbens.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 107 citations in OpenAlex.
- ECM remodeling in the mPFC exacerbates cocaine-induced hyperactivity and impairs threat vigilance.Translational psychiatry · 2026Article
- Addictive drug abuse and depression-a focus on epigenetics.Communications biology · 2026Review
- Elucidating the molecular symphony: unweaving the transcriptional & epigenetic pathways underlying neuroplasticity in opioid dependence and withdrawal.Psychopharmacology · 2024Review
- SIRT1 Coordinates Transcriptional Regulation of Neural Activity and Modulates Depression-Like Behaviors in the Nucleus Accumbens.Biological psychiatry · 2024Article
- Sex-Specific ADNP/NAP (Davunetide) Regulation of Cocaine-Induced Plasticity.Journal of molecular neuroscience : MN · 2024Article
- Loss of FoxO1 activates an alternate mechanism of mitochondrial quality control for healthy adipose browning.Clinical science (London, England : 1979) · 2024Article
- Activation of AMPK/SIRT1/FOXO3a signaling by BMS-477118 (saxagliptin) mitigates chronic colitis in rats: uncovering new anti-inflammatory and antifibrotic roles.Frontiers in pharmacology · 2024Article
- Therapeutic Consequences of Targeting the IGF-1/PI3K/AKT/FOXO3 Axis in Sarcopenia: A Narrative Review.Cells · 2023Review
- Functional study and epigenetic targets analyses ofEpigenetics · 2023Article
- The citrus flavonoid "Nobiletin" impedes STZ-induced Alzheimer's disease in a mouse model through regulating autophagy mastered by SIRT1/FoxO3a mechanism.Inflammopharmacology · 2023Article
- Differential Effects of Cocaine and Morphine on the Diurnal Regulation of the Mouse Nucleus Accumbens Proteome.Journal of proteome research · 2023Article
- Review
- The Association between Blood SIRT1 and Ghrelin, Leptin, and Antibody Anti-Hypothalamus: A Comparison in Normal Weight and Anorexia Nervosa.Journal of personalized medicine · 2023Article
- Abstinence from Escalation of Cocaine Intake Changes the microRNA Landscape in the Cortico-Accumbal Pathway.Biomedicines · 2023Article
- How can nanomicelle-curcumin modulate aluminum phosphide-induced neurotoxicity?: Role of SIRT1/FOXO3 signaling pathway.AIMS neuroscience · 2023Article
- Allicin and Capsaicin Ameliorated Hypercholesterolemia by Upregulating LDLR and Downregulating PCSK9 Expression in HepG2 Cells.International journal of molecular sciences · 2022Article
- Article
- A Role for Histone Deacetylases in the Biology and Treatment of Post-Traumatic Stress Disorder: What Do We Know and Where Do We Go from Here?Complex psychiatry · 2022Review
- Uterine-specific SIRT1 deficiency confers premature uterine aging and impairs invasion and spacing of blastocyst, and stromal cell decidualization, in mice.Molecular human reproduction · 2022Article
- eNAMPT actions through nucleus accumbens NADScience advances · 2022Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Previous studies have shown that chronic cocaine administration induces SIRT1, a Class III histone deacetylase, in the nucleus accumbens (NAc), a key brain reward region, and that such induction influences the gene regulation and place conditioning effects of cocaine. To determine the mechanisms by which SIRT1 mediates cocaine-induced plasticity in NAc, we used chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-seq), 1 d after 7 daily cocaine (20 mg/kg) or saline injections, to map SIRT1 binding genome-wide in mouse NAc. Our unbiased results revealed two modes of SIRT1 action. First, despite its induction in NAc, chronic cocaine causes depletion of SIRT1 from most affected gene promoters in concert with enrichment of H4K16ac (itself a deacetylation target of SIRT1), which is associated with increased expression of these genes. Second, we deduced the forkhead transcription factor (FOXO) family to be a downstream mechanism through which SIRT1 regulates cocaine action. We proceeded to demonstrate that SIRT1 induction causes the deacetylation and activation of FOXO3a in NAc, which leads to the induction of several known FOXO3a gene targets in other systems. Finally, we directly establish a role for FOXO3a in promoting cocaine-elicited behavioral responses by use of viral-mediated gene transfer: we show that overexpressing FOXO3a in NAc enhances cocaine place conditioning. The discovery of these two actions of SIRT1 in NAc in the context of behavioral adaptations to cocaine represents an important step forward in advancing our understanding of the molecular adaptations underlying cocaine action.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.