Send to

Choose Destination
Neuron. 2017 Dec 20;96(6):1327-1341.e6. doi: 10.1016/j.neuron.2017.11.037.

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

Author information

Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, USA.
Department of Pharmacology and Toxicology, The Research Institution on Addictions, State University of New York at Buffalo, Buffalo, NY, USA.
Division of Renal Diseases and Hypertension, The George Washington University, Washington, D.C., USA.
Fishberg Department of Neuroscience and Friedman Brain Institute, Graduate School of Biomedical Sciences at the Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Psychology, University of Texas at El Paso, El Paso, TX, USA.
McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montréal, QC, Canada.
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address:


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.


Drp1; cocaine; medium spiny neurons; mitochondria; nucleus accumbens; self-administration

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center