CBP in the nucleus accumbens regulates cocaine-induced histone acetylation and is critical for cocaine-associated behaviors.
paper
Cited
Public
Unavailable
- Authors
- Malvaez, Melissa; Mhillaj, Emanuela; Matheos, Dina P; Palmery, Maura; Wood, Marcelo A
- Year
- 2011
- Journal
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- PMID
- 22114264
- DOI
- 10.1523/JNEUROSCI.2747-11.2011
- PMCID
- PMC3235434
Cocaine exposure triggers molecular events that lead to long-lasting changes in brain structure and function. These changes can lead to the development of persistent and robust behavioral adaptations that characterize addiction. Recent evidence suggests the regulation of transcription via chromatin modification, such as histone acetylation, has an important role in the development of addictive behavior. Histone acetylation is regulated by histone acetyltransferases (HATs), which acetylate histones and promote transcription, and histone deacetylases (HDACs), which remove acetyl groups and silence transcription. Studies have demonstrated that HDACs may negatively regulate cocaine-induced behaviors, but very little is known about the role of specific HATs in long-lasting drug-induced plasticity. The histone acetyltransferase CREB-binding protein (CBP) mediates transcriptional activation by recruiting basal transcription machinery and acetylating histones. CBP is a critically important chromatin-modifying enzyme involved in regulating gene expression required for long-term plasticity and memory. However, the role of CBP in cocaine-induced behaviors remains largely unknown. We examined the role of CBP in drug-induced plasticity using CBP-FLOX genetically modified mice in combination with adeno-associated virus expressing Cre-recombinase to generate focal homozygous deletions of Cbp in the nucleus accumbens (NAc). A complete loss of CBP in NAc neurons results in decreased histone acetylation and significantly altered c-fos expression in response to cocaine. Furthermore, the deletion of CBP in the NAc correlates with significant impairments in cocaine sensitivity and context-cocaine associated memory. This is the first study to demonstrate a definitive role for CBP in modulating gene expression that may subserve drug-seeking behaviors.
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| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Addictive drug abuse and depression-a focus on epigenetics. | Zhang W et al. | β | 2026 | β |
| CREB-Binding Protein Regulates Cocaine- and Amphetamine-Regulated Transcript Peptide Expression in the Lateral Hypothalamus: Implication in Reward and Reinforcement. | Pawar N et al. | β | 2025 | β |
| Molecular and genetic mechanisms of plasticity in addiction. | Brida KL et al. | β | 2025 | β |
| Drug addiction and treatment: An epigenetic perspective. | Koijam AS et al. | β | 2024 | β |
| Epigenetic mechanisms of nicotine dependence. | Muenstermann C et al. | β | 2024 | β |
| Genomic factors associated with substance use disorder relapse: A critical review. | Al-Marzooqi N et al. | β | 2024 | β |
| How life events may confer vulnerability to addiction: the role of epigenetics. | Liu SX et al. | β | 2024 | β |
| The single-cell opioid responses in the context of HIV (SCORCH) consortium. | Ament SA et al. | β | 2024 | β |
| Bromodomain and Extra-Terminal Proteins in Brain Physiology and Pathology: BET-ing on Epigenetic Regulation. | Martella N et al. | β | 2023 | β |
| Epigenetic modification impacting brain functions: Effects of physical activity, micronutrients, caffeine, toxins, and addictive substances. | Mallick R et al. | β | 2023 | β |
| Histone modifications in cocaine, methamphetamine and opioids. | Cheng J et al. | β | 2023 | β |
| Morphine-withdrawal aversive memories and their extinction modulate H4K5 acetylation and Brd4 activation in the rat hippocampus and basolateral amygdala. | Franco-GarcΓa A et al. | β | 2023 | β |
| Domain-selective BET inhibition attenuates transcriptional and behavioral responses to cocaine. | Singh MB et al. | β | 2022 | β |
| Epigenetic Effects of Addictive Drugs in the Nucleus Accumbens. | Anderson EM et al. | β | 2022 | β |
| Epigenetic Modulation of Opioid Receptors by Drugs of Abuse. | Reid KZ et al. | β | 2022 | β |
| Antisense-induced knockdown of cAMP response element-binding protein downregulates Per1 gene expression in the shell region of nucleus accumbens resulting in reduced alcohol consumption in mice. | Sharma R et al. | β | 2021 | β |
| Behavioral sensitization induced by methamphetamine causes differential alterations in gene expression and histone acetylation of the prefrontal cortex in rats. | Li H et al. | β | 2021 | β |
| Domain-selective BET inhibition attenuates transcriptional and behavioral responses to cocaine | Singh M et al. | β | 2021 | β |
| Drug addiction: from bench to bedside. | Cheron J et al. | β | 2021 | β |
| Dynamic subcellular localization and transcription activity of the SRF cofactor MKL2 in the striatum are regulated by MAPK. | Ariza A et al. | β | 2021 | β |
| Epigenetics of addiction. | Cadet JL et al. | β | 2021 | β |
| Exercise Reduces H3K9me3 and Regulates Brain Derived Neurotrophic Factor and GABRA2 in an Age Dependent Manner. | Ionescu-Tucker A et al. | β | 2021 | β |
| HDAC3 Activity within the Nucleus Accumbens Regulates Cocaine-Induced Plasticity and Behavior in a Cell-Type-Specific Manner. | Campbell RR et al. | β | 2021 | β |
| Psychostimulants and opioids differentially influence the epigenetic modification of histone acetyltransferase and histone deacetylase in astrocytes. | Doke M et al. | β | 2021 | β |
| The Mechanisms and Boundary Conditions of Drug Memory Reconsolidation. | Chen L et al. | β | 2021 | β |
| The Signaling and Pharmacology of the Dopamine D1 Receptor. | Jones-Tabah J et al. | β | 2021 | β |
| Activity-Dependent Epigenetic Remodeling in Cocaine Use Disorder. | LΓ³pez AJ et al. | β | 2020 | β |
| BET bromodomains as novel epigenetic targets for brain health and disease. | Singh MB et al. | β | 2020 | β |
| Molecular and circuit mechanisms regulating cocaine memory. | Bender BN et al. | β | 2020 | β |
| The Emerging Role of ATP-Dependent Chromatin Remodeling in Memory and Substance Use Disorders. | LΓ³pez AJ et al. | β | 2020 | β |
| Distinct cortical-amygdala projections drive reward value encoding and retrieval. | Malvaez M et al. | β | 2019 | β |
| Epigenetic pharmacotherapy for substance use disorder. | Sartor GC | β | 2019 | β |
| Epigenetic regulation of immediate-early gene Nr4a2/Nurr1 in the medial habenula during reinstatement of cocaine-associated behavior. | LΓ³pez AJ et al. | β | 2019 | β |
| Epigenetics and addiction. | Hamilton PJ et al. | β | 2019 | β |
| How the epigenome integrates information and reshapes the synapse. | Campbell RR et al. | β | 2019 | β |
| It is a complex issue: emerging connections between epigenetic regulators in drug addiction. | Anderson EM et al. | β | 2019 | β |
| Medial habenula cholinergic signaling regulates cocaine-associated relapse-like behavior. | LΓ³pez AJ et al. | β | 2019 | β |
| Phosphorylation of Npas4 by MAPK Regulates Reward-Related Gene Expression and Behaviors. | Funahashi Y et al. | β | 2019 | β |
| Sex-Specific Regulation of Fear Memory by Targeted Epigenetic Editing of Cdk5. | Sase AS et al. | β | 2019 | β |
| The crayfish model (Orconectes rusticus), epigenetics and drug addiction research. | Imeh-Nathaniel A et al. | β | 2019 | β |
| CREST in the Nucleus Accumbens Core Regulates Cocaine Conditioned Place Preference, Cocaine-Seeking Behavior, and Synaptic Plasticity. | Alaghband Y et al. | β | 2018 | β |
| Habits Are Negatively Regulated by Histone Deacetylase 3 in the Dorsal Striatum. | Malvaez M et al. | β | 2018 | β |
| Neuroepigenetics and addiction. | Walker DM et al. | β | 2018 | β |
| Persistent histone modifications at the BDNF and Cdk-5 promoters following extinction of nicotine-seeking in rats. | Castino MR et al. | β | 2018 | β |
| Role of Dorsal Striatum Histone Deacetylase 5 in Incubation of Methamphetamine Craving. | Li X et al. | β | 2018 | β |
| A Role for Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1Ξ± in Nucleus Accumbens Neuron Subtypes in Cocaine Action. | Chandra R et al. | β | 2017 | β |
| Chronic ΞβΈ-THC Exposure Differently Affects Histone Modifications in the Adolescent and Adult Rat Brain. | Prini P et al. | β | 2017 | β |
| Cracking the pathogenesis of cocaine-induced vasculitis. | Pieterse E et al. | β | 2017 | β |
| Distinct roles for the deacetylase domain of HDAC3 in the hippocampus and medial prefrontal cortex in the formation and extinction of memory. | Alaghband Y et al. | β | 2017 | β |
| Epigenetics: a link between addiction and social environment. | Ajonijebu DC et al. | β | 2017 | β |
| BDNF rescues BAF53b-dependent synaptic plasticity and cocaine-associated memory in the nucleus accumbens. | White AO et al. | β | 2016 | β |
| Dysregulation of Acetylation Enzymes Inanimal Models of Psychostimulant use Disorders: Evolving Stories. | Lud Cadet J | β | 2016 | β |
| Epigenetics and addiction. | Cadet JL et al. | β | 2016 | β |
| Epigenetics of Stress, Addiction, and Resilience: Therapeutic Implications. | Cadet JL | β | 2016 | β |
| Involvement of phosphorylated Apis mellifera CREB in gating a honeybee's behavioral response to an external stimulus. | Gehring KB et al. | β | 2016 | β |
| KAT2B polymorphism identified for drug abuse in African Americans with regulatory links to drug abuse pathways in human prefrontal cortex. | Johnson EO et al. | β | 2016 | β |
| Overexpression of SIRT6 in the hippocampal CA1 impairs the formation of long-term contextual fear memory. | Yin X et al. | β | 2016 | β |
| Rescuing prefrontal cAMP-CREB pathway reverses working memory deficits during withdrawal from prolonged alcohol exposure. | Dominguez G et al. | β | 2016 | β |
| Sensory Cortical Plasticity Participates in the Epigenetic Regulation of Robust Memory Formation. | Phan ML et al. | β | 2016 | β |
| Transgenerational Inheritance of Paternal Neurobehavioral Phenotypes: Stress, Addiction, Ageing and Metabolism. | Yuan TF et al. | β | 2016 | β |
| Aberrant Monoaminergic System in Thyroid Hormone Receptor-Ξ² Deficient Mice as a Model of Attention-Deficit/Hyperactivity Disorder. | Ookubo M et al. | β | 2015 | β |
| CAMKII-conditional deletion of histone deacetylase 2 potentiates acute methamphetamine-induced expression of immediate early genes in the mouse nucleus accumbens. | Torres OV et al. | β | 2015 | β |
| Epigenetic Mechanisms of Psychostimulant-Induced Addiction. | Kalda A et al. | β | 2015 | β |
| Epigenetic Readers of Lysine Acetylation Regulate Cocaine-Induced Plasticity. | Sartor GC et al. | β | 2015 | β |
| Inhibition of histone deacetylase in the basolateral amygdala facilitates morphine context-associated memory formation in rats. | Wang Y et al. | β | 2015 | β |
| Inhibition of histone deacetylases facilitates extinction and attenuates reinstatement of nicotine self-administration in rats. | Castino MR et al. | β | 2015 | β |
| Neuroepigenetic Regulation of Pathogenic Memories. | Daws SE et al. | β | 2015 | β |
| Regulation of chromatin states by drugs of abuse. | Walker DM et al. | β | 2015 | β |
| Vitamin D receptor and epigenetics in HIV infection and drug abuse. | Chandel N et al. | β | 2015 | β |
| Epigenetic mechanisms of drug addiction. | Nestler EJ | β | 2014 | β |
| Epigenetic signaling in psychiatric disorders. | PeΓ±a CJ et al. | β | 2014 | β |
| Learning induced epigenetic modifications in the ventral striatum are necessary for long-term memory. | Gaglio D et al. | β | 2014 | β |
| Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors. | Heller EA et al. | β | 2014 | β |
| Methamphetamine-associated memory is regulated by a writer and an eraser of permissive histone methylation. | Aguilar-Valles A et al. | β | 2014 | β |
| The epigenetic landscape of alcoholism. | Krishnan HR et al. | β | 2014 | β |
| Alcohol-induced histone acetylation reveals a gene network involved in alcohol tolerance. | Ghezzi A et al. | β | 2013 | β |
| Chronic co-administration of nicotine and methamphetamine causes differential expression of immediate early genes in the dorsal striatum and nucleus accumbens of rats. | Saint-Preux F et al. | β | 2013 | β |
| Class I HDAC inhibition blocks cocaine-induced plasticity by targeted changes in histone methylation. | Kennedy PJ et al. | β | 2013 | β |
| HDAC3 is a negative regulator of cocaine-context-associated memory formation. | Rogge GA et al. | β | 2013 | β |
| HDAC3-selective inhibitor enhances extinction of cocaine-seeking behavior in a persistent manner. | Malvaez M et al. | β | 2013 | β |
| Nicotine primes the effect of cocaine on the induction of LTP in the amygdala. | Huang YY et al. | β | 2013 | β |
| Nuclear calcium signalling in the regulation of brain function. | Bading H | β | 2013 | β |
| Possible contributions of a novel form of synaptic plasticity in Aplysia to reward, memory, and their dysfunctions in mammalian brain. | Hawkins RD | β | 2013 | β |
| Sodium butyrate-induced histone acetylation strengthens the expression of cocaine-associated contextual memory. | Itzhak Y et al. | β | 2013 | β |
| The histone deacetylase inhibitor sodium butyrate modulates acquisition and extinction of cocaine-induced conditioned place preference. | Raybuck JD et al. | β | 2013 | β |
| The role of histone acetylation in cocaine-induced neural plasticity and behavior. | Rogge GA et al. | β | 2013 | β |
| Understanding stress-effects in the brain via transcriptional signal transduction pathways. | Zalachoras I et al. | β | 2013 | β |
| Extinction of aversive memories associated with morphine withdrawal requires ERK-mediated epigenetic regulation of brain-derived neurotrophic factor transcription in the rat ventromedial prefrontal cortex. | Wang WS et al. | β | 2012 | β |
| G9a/GLP histone lysine dimethyltransferase complex activity in the hippocampus and the entorhinal cortex is required for gene activation and silencing during memory consolidation. | Gupta-Agarwal S et al. | β | 2012 | β |
| Molecular brake pad hypothesis: pulling off the brakes for emotional memory. | Vogel-Ciernia A et al. | β | 2012 | β |
| Neuroplasticity in addiction: cellular and transcriptional perspectives. | Madsen HB et al. | β | 2012 | β |
| Serum starvation induces DRAM expression in liver cancer cells via histone modifications within its promoter locus. | Ni P et al. | β | 2012 | β |