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

被引：72

作者：

Chandra, Ramesh ^{[1
]}

Engeln, Michel ^{[1
]}

Schiefer, Christopher ^{[1
]}

Patton, Mary H. ^{[2
]}

Martin, Jennifer A. ^{[3
]}

Werner, Craig T. ^{[3
]}

Riggs, Lace M. ^{[1
]}

Francis, T. Chase ^{[1
]}

McGlincy, Madeleine ^{[1
]}

Evans, Brianna ^{[1
]}

Nam, Hyungwoo ^{[1
]}

Das, Shweta ^{[1
]}

Girven, Kasey ^{[1
]}

Konkalmatt, Prasad ^{[4
]}

Gancarz, Amy M. ^{[3
]}

Golden, Sam A. ^{[5
,6
]}

Iniguez, Sergio D. ^{[7
]}

Russo, Scott J. ^{[5
,6
]}

Turecki, Gustavo ^{[8
]}

Mathur, Brian N. ^{[2
]}

Creed, Meaghan ^{[2
]}

Dietz, David M. ^{[3
]}

Lobo, Mary Kay ^{[1
]}

机构：

[1] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA

[2] Univ Maryland, Sch Med, Dept Pharmacol, Baltimore, MD 21201 USA

[3] SUNY Buffalo, Res Inst Addict, Dept Pharmacol & Toxicol, Buffalo, NY USA

[4] George Washington Univ, Div Renal Dis & Hypertens, Washington, DC USA

[5] Icahn Sch Med Mt Sinai, Grad Sch Biomed Sci, Fishberg Dept Neurosci, New York, NY 10029 USA

[6] Icahn Sch Med Mt Sinai, Grad Sch Biomed Sci, Friedman Brain Inst, New York, NY 10029 USA

[7] Univ Texas El Paso, Dept Psychol, El Paso, TX 79968 USA

[8] McGill Univ, Douglas Mental Hlth Univ Inst, McGill Grp Suicide Studies, Montreal, PQ, Canada

来源：

NEURON | 2017年 / 96卷 / 06期

关键词：

MEDIUM SPINY NEURONS; RAT-BRAIN STRUCTURES; NUCLEUS-ACCUMBENS; DELTA-FOSB; STRESS SUSCEPTIBILITY; PREFRONTAL CORTEX; SYNAPSE FORMATION; INDIRECT PATHWAYS; CRE-RECOMBINASE; OUTER-MEMBRANE;

D O I：

10.1016/j.neuron.2017.11.037

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：1327 / +

页数：21

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