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

TitleDrp1 Mitochondrial Fission in D1 Neurons Mediates Behavioral and Cellular Plasticity during Early Cocaine Abstinence.
Publication TypeJournal Article
Year of Publication2017
AuthorsChandra R, Engeln M, Schiefer C, Patton MH, Martin JA, Werner CT, Riggs LM, T Francis C, McGlincy M, Evans B, Nam H, Das S, Girven K, Konkalmatt P, Gancarz AM, Golden SA, Iniguez SD, Russo SJ, Turecki G, Mathur BN, Creed M, Dietz DM, Lobo MKay
JournalNeuron
Volume96
Issue6
Pagination1327-1341.e6
Date Published2017 Dec 20
ISSN1097-4199
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.

DOI10.1016/j.neuron.2017.11.037
Alternate JournalNeuron
PubMed ID29268097
PubMed Central IDPMC5747376
Grant ListR01 DA037257 / DA / NIDA NIH HHS / United States
SC2 GM109811 / GM / NIGMS NIH HHS / United States
R25 GM055036 / GM / NIGMS NIH HHS / United States
R01 AA024845 / AA / NIAAA NIH HHS / United States
R01 DA038613 / DA / NIDA NIH HHS / United States