A novel role for the actin-binding protein drebrin in regulating opiate addiction

Jennifer A. Martin, Craig T. Werner, Swarup Mitra, Ping Zhong, Zi Jun Wang, Pedro H. Gobira, Andrew F. Stewart, Jay Zhang, Kyra Erias, Justin N. Siemian, Devin Hagarty, Lauren E. Mueller, Rachael L. Neve, Jun Xu Li, Ramesh Chandra, Karen C. Dietz, Mary Kay Lobo, Amy M. Gancarz, Zhen Yan, David M. Dietz

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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.

Original languageEnglish
Article number4140
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - 1 Dec 2019
Externally publishedYes

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