A Novel Role for Oligodendrocyte Precursor Cells (OPCs) and Sox10 in Mediating Cellular and Behavioral Responses to Heroin

Jennifer A. Martin, Aaron Caccamise, Craig T. Werner, Rathipriya Viswanathan, Jessie J. Polanco, Andrew F. Stewart, Shruthi A. Thomas, Fraser J. Sim, David M. Dietz

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Opiate abuse and addiction have become a worldwide epidemic with great societal and financial burdens, highlighting a critical need to understand the neurobiology of opiate addiction. Although several studies have focused on drug-dependent changes in neurons, the role of glia in opiate addiction remains largely unstudied. RNA sequencing pathway analysis from the prefrontal cortex (PFC) of male rats revealed changes in several genes associated with oligodendrocyte differentiation and maturation following heroin self-administration. Among these genes changed was Sox10, which is regulated, in part, by the chromatin remodeler BRG1/SMARCA4. To directly test the functional role of Sox10 in mediating heroin-induced behavioral plasticity, we selectively overexpressed Sox10 and BRG1 in the PFC. Overexpression of either Sox10 or BRG1 decreased the motivation to obtain heroin infusions in a progressive ratio test without altering the acquisition or maintenance of heroin self-administration. These data demonstrate a critical, and perhaps compensatory, role of Sox10 and BRG1 in oligodendrocytes in regulating the motivation for heroin.

Original languageEnglish
Pages (from-to)1385-1394
Number of pages10
JournalNeuropsychopharmacology
Volume43
Issue number6
DOIs
StatePublished - 1 May 2018
Externally publishedYes

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