Nature communications, 2019-09, Vol.10 (1), p.4140-11, Article 4140
2019
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- Autor(en) / Beteiligte
- Titel
- A novel role for the actin-binding protein drebrin in regulating opiate addiction
- Ist Teil von
- Nature communications, 2019-09, Vol.10 (1), p.4140-11, Article 4140
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Persistent transcriptional and morphological events in the nucleus accumbens (NAc) and other brain reward regions contribute to the long-lasting behavioral adaptations that characterize drug addiction. Opiate exposure reduces the density of dendritic spines on medium spiny neurons of the NAc; however, the underlying transcriptional and cellular events mediating this remain unknown. We show that heroin self-administration negatively regulates the actin-binding protein drebrin in the NAc. Using virus-mediated gene transfer, we show that drebrin overexpression in the NAc is sufficient to decrease drug seeking and increase dendritic spine density, whereas drebrin knockdown potentiates these effects. We demonstrate that drebrin is transcriptionally repressed by the histone modifier HDAC2, which is relieved by pharmacological inhibition of histone deacetylases. Importantly, we demonstrate that heroin-induced adaptations occur only in the D1 subset of medium spiny neurons. These findings establish an essential role for drebrin, and upstream transcriptional regulator HDAC2, in opiate-induced plasticity in the NAc.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-019-12122-8Titel-ID: cdi_doaj_primary_oai_doaj_org_article_fd3986183cd145e696e221b400cee251
- Format
- –
- Schlagworte
- Actin, Adaptations, Animals, Behavior, Animal - drug effects, Behavioral plasticity, Dendritic spines, Density, Drug abuse, Drug addiction, Drug self-administration, Epigenesis, Genetic - drug effects, Gene transfer, HDAC2 protein, Heroin, Heroin - adverse effects, Histone deacetylase, Histone Deacetylase 2 - metabolism, Histones, Male, Microfilament Proteins - metabolism, Narcotics, Neuronal Plasticity - drug effects, Neurons, Neurons - drug effects, Neurons - metabolism, Neuropeptides - genetics, Neuropeptides - metabolism, Nucleus accumbens, Nucleus Accumbens - metabolism, Opiate Alkaloids - adverse effects, Opioid-Related Disorders - metabolism, Opioid-Related Disorders - physiopathology, Pain - metabolism, Proteins, Rats, Sprague-Dawley, Reinforcement, Spine, Spiny neurons, Synapses - drug effects, Synapses - metabolism, Transcription, Viruses