A novel role for the actin-binding protein drebrin in regulating opiate addiction
PublisherNature Publishing Group
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AbstractPersistent 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. Copyright 2019, The Author(s).
SponsorsThis work was supported by the National Institutes of Health (no. NIDA R01DA037257, NIDA R01DA037257-S1, NIDA R21DA044486, NIDA R01DA046818, NIDA R01DA038613, NIDA R01DA037618, NINDS F99NS108543, and NIGMS R25GM09545902).
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85072150420&doi=10.1038%2fs41467-019-12122-8&partnerID=40&md5=52f93cf30ce635865e5c75e6c6caf989; http://hdl.handle.net/10713/11169