ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Activation of CREB in the nucleus accumbens shell produces anhedonia and resistance to extinction of fear in 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 62 papers.
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Who cites it
62 citing papers in PubMed, 100 citations in OpenAlex.
- Computationally Informed Insights Into Anhedonia and Treatment by Kappa Opioid Receptor Antagonism.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2025Trial
- A randomized proof-of-mechanism trial applying the 'fast-fail' approach to evaluating κ-opioid antagonism as a treatment for anhedonia.Nature medicine · 2020Trial
- Stress-induced adaptations in nucleus accumbens dopamine D1 receptor-expressing cells correspond to social avoidance behavior in male mice.IBRO neuroscience reports · 2026Article
- Stress-induced reinstatement of nicotine conditioned place preference in a rodent model of dopamine dysregulation: genetic, behavioral and molecular correlates of drug abuse vulnerability.Psychopharmacology · 2026Article
- Article
- Altered Expression of Neuroplasticity-Related Genes in Alcohol Addiction and Treatment.International journal of molecular sciences · 2024Article
- Opioid Mechanisms and the Treatment of Depression.Current topics in behavioral neurosciences · 2024Review
- The opioid system in depression.Neuroscience and biobehavioral reviews · 2022Review
- Kappa Opioid Receptors in the Pathology and Treatment of Major Depressive Disorder.Handbook of experimental pharmacology · 2022Review
- Anhedonia in Posttraumatic Stress Disorder: Prevalence, Phenotypes, and Neural Circuitry.Current topics in behavioral neurosciences · 2022Review
- Dissociable roles of the nucleus accumbens core and shell subregions in the expression and extinction of conditioned fear.Neurobiology of stress · 2021Article
- Nucleus Accumbens Medium Spiny Neuron Subtypes Differentially Regulate Stress-Associated Alterations in Sleep Architecture.Biological psychiatry · 2021Article
- Stress-induced alterations of mesocortical and mesolimbic dopaminergic pathways.Scientific reports · 2021Article
- The NIMH 'Fast-Fail Trials' (FAST) Initiative: Rationale, Promise, and Progress.Pharmaceutical medicine · 2020Review
- Dezocine Alleviates Morphine-Induced Dependence in Rats.Anesthesia and analgesia · 2019Article
- Pain And Opioid Systems, Implications In The Opioid Epidemic.Current opinion in behavioral sciences · 2019Article
- Kappa opioid receptors mediate yohimbine-induced increases in impulsivity in the 5-choice serial reaction time task.Behavioural brain research · 2019Article
- Transcriptional Regulation Involved in Fear Memory Reconsolidation.Journal of molecular neuroscience : MN · 2018Review
- Fear extinction requires infralimbic cortex projections to the basolateral amygdala.Translational psychiatry · 2018Article
- Lateral orbitofrontal cortex partitions mechanisms for fear regulation and alcohol consumption.PloS one · 2018Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Stress triggers psychiatric conditions including depressive and anxiety disorders. The mechanisms by which stress produces persistent changes in behavior are not fully understood. Here we show in rats that stress (footshock) activates the transcription factor cAMP response element binding protein (CREB) within the nucleus accumbens shell (NAS), a brain area involved in encoding reward and aversion. To examine the behavioral significance of altered CREB function in the NAS, we used viral vectors to elevate or disrupt CREB in this region. Elevated CREB produced increases in intracranial self-stimulation thresholds, a depressive-like sign reflecting anhedonia (decreased sensitivity to reward), whereas disruption of CREB function by expression of a dominant-negative CREB had the opposite effect. To determine whether neuroadaptations that produce anhedonia subsequently affect vulnerability to stress-induced behavioral adaptations, we subjected rats with altered CREB function in the NAS to fear conditioning. Although neither elevation nor disruption of CREB function altered the development of conditioned fear, elevation of CREB impaired extinction of conditioned fear. To mimic downstream effects of CREB activation on expression of the opioid peptide dynorphin, we microinjected the κ-opioid receptor (KOR) agonist U50,488 directly into the NAS. KOR stimulation produced anhedonia but had no effect on expression or extinction of conditioned fear. These findings demonstrate that activation of CREB in the NAS produces multiple behavioral signs (anhedonia, impaired extinction) characteristic of experience-dependent psychiatric conditions such as posttraumatic stress disorder. Although CREB activation is a common trigger, expression of these individual signs appears to involve divergent downstream mechanisms.
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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.