Drp1 Mitochondrial Fission in D1 Neurons Mediates Behavioral and Cellular Plasticity During Early Cocaine Abstinence

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2017 Dec 22

PMID 29268097

Citations 57

Authors

Ramesh Chandra

Michel Engeln

Christopher Schiefer

Mary H Patton

Jennifer A Martin

Craig T Werner

Lace M Riggs

T Chase Francis

Madeleine McGlincy

Brianna Evans

Hyungwoo Nam

Shweta Das

Kasey Girven

Prasad Konkalmatt

Amy M Gancarz

Sam A Golden

Sergio D Iniguez

Scott J Russo

Gustavo Turecki

Brian N Mathur

Meaghan Creed

David M Dietz

Mary Kay Lobo

Affiliations

Soon will be listed here.

Abstract

Altered brain energy homeostasis is a key adaptation occurring in the cocaine-addicted brain, but the effect of cocaine on the fundamental source of energy, mitochondria, is unknown. We demonstrate an increase of dynamin-related protein-1 (Drp1), the mitochondrial fission mediator, in nucleus accumbens (NAc) after repeated cocaine exposure and in cocaine-dependent individuals. Mdivi-1, a demonstrated fission inhibitor, blunts cocaine seeking and locomotor sensitization, while blocking c-Fos induction and excitatory input onto dopamine receptor-1 (D1) containing NAc medium spiny neurons (MSNs). Drp1 and fission promoting Drp1 are increased in D1-MSNs, consistent with increased smaller mitochondria in D1-MSN dendrites after repeated cocaine. Knockdown of Drp1 in D1-MSNs blocks drug seeking after cocaine self-administration, while enhancing the fission promoting Drp1 enhances seeking after long-term abstinence from cocaine. We demonstrate a role for altered mitochondrial fission in the NAc, during early cocaine abstinence, suggesting potential therapeutic treatment of disrupting mitochondrial fission in cocaine addiction.

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