ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Overexpression of CREB in the nucleus accumbens shell increases cocaine reinforcement in self-administering rats.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 131 citations in OpenAlex.
- Depleting retinoic acid synthesis in the nucleus accumbens shell produces a protective phenotype for emotional reactivity and drug-taking in rats.Psychopharmacology · 2026Article
- Astrocytic CREB regulates transcriptomic, neuronal, and behavioral responses to cocaine.Science advances · 2025Article
- Projection-defined ventral tegmental area neurons exhibit fentanyl-induced molecular and functional adaptations that differentially support drug-context associations.bioRxiv : the preprint server for biology · 2025Article
- Drug-Related Engrams and Their Role in the Persistence and Recurrence of Drug-Related Behaviors.Hippocampus · 2025Review
- Cocaine-induced gene regulation in D1 and D2 neuronal ensembles of the nucleus accumbens.Communications biology · 2025Article
- Astrocytic CREB in Nucleus Accumbens Promotes Susceptibility to Chronic Stress.Biological psychiatry · 2025Article
- The universal role of adaptive transcription in health and disease.The FEBS journal · 2025Review
- Article
- Cell type-specific epigenetic priming of gene expression in nucleus accumbens by cocaine.Science advances · 2024Article
- NMDA receptor within nucleus accumbens shell regulates propofol self-administration through D1R/ERK/CREB signalling pathway.Addiction biology · 2024Article
- Astrocytic CREB in nucleus accumbens promotes susceptibility to chronic stress.bioRxiv : the preprint server for biology · 2024Article
- Adolescent circadian rhythm disruption increases reward and risk-taking.Frontiers in neuroscience · 2024Article
- Convergent abnormalities in striatal gene networks in human cocaine use disorder and mouse cocaine administration models.Science advances · 2023Article
- Fibroblast growth factor 13-mediated regulation of medium spiny neuron excitability and cocaine self-administration.Frontiers in neuroscience · 2023Article
- Distinct forms of regret linked to resilience versus susceptibility to stress are regulated by region-specific CREB function in mice.Science advances · 2022Article
- Inactivation of the Lateral Hypothalamus Attenuates Methamphetamine-Induced Conditioned Place Preference through Regulation of Kcnq3 Expression.International journal of molecular sciences · 2022Article
- Addiction-induced plasticity in underlying neural circuits.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022Review
- Key transcription factors mediating cocaine-induced plasticity in the nucleus accumbens.Molecular psychiatry · 2022Review
- Importin α3 (KPNA3) Deficiency Augments Effortful Reward-Seeking Behavior in Mice.Frontiers in neuroscience · 2022Article
- Epigenetics of Drug Addiction.Cold Spring Harbor perspectives in medicine · 2021Review
23 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
Abstract
Chronic exposure to addictive drugs enhances cAMP response element binding protein (CREB)-regulated gene expression in nucleus accumbens (NAc), and these effects are thought to reduce the positive hedonic effects of passive cocaine administration. Here, we used viral-mediated gene transfer to produce short- and long-term regulation of CREB activity in NAc shell of rats engaging in volitional cocaine self-administration. Increasing CREB expression in NAc shell markedly enhanced cocaine reinforcement of self-administration behavior, as indicated by leftward (long-term) and upward (short-term) shifts in fixed ratio dose-response curves. CREB also increased the effort exerted by rats to obtain cocaine on more demanding progressive ratio schedules, an effect highly correlated with viral-induced modulation of BDNF protein in the NAc shell. CREB enhanced cocaine reinforcement when expressed either throughout acquisition of self-administration or when expression was limited to postacquisition tests, indicating a direct effect of CREB independent of reinforcement-related learning. Downregulating endogenous CREB in NAc shell by expressing a short hairpin RNA reduced cocaine reinforcement in similar tests, while overexpression of a dominant-negative CREB(S133A) mutant had no significant effect on cocaine self-administration. Finally, increasing CREB expression after withdrawal from self-administration enhanced cocaine-primed relapse, while reducing CREB levels facilitated extinction of cocaine seeking, but neither altered relapse induced by cocaine cues or footshock stress. Together, these findings indicate that CREB activity in NAc shell increases the motivation for cocaine during active self-administration or after withdrawal from cocaine. Our results also highlight that volitional and passive drug administration can lead to substantially different behavioral outcomes.
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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.