Drp1 Mitochondrial Fission in D1 Neurons Mediates Behavioral and Cellular Plasticity during Early Cocaine Abstinence
| Autor: | Michel Engeln, Shweta Das, Brianna Evans, Scott J. Russo, Jennifer A. Martin, Sam A. Golden, Sergio D. Iñiguez, Ramesh Chandra, Brian N. Mathur, Meaghan C. Creed, Christopher Schiefer, Amy M. Gancarz, Craig T. Werner, T. Chase Francis, Gustavo Turecki, Mary Kay Lobo, Prasad Konkalmatt, David M. Dietz, Lace M. Riggs, Mary H. Patton, Madeleine McGlincy, Kasey S. Girven, Hyungwoo Nam |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Dynamins endocrine system media_common.quotation_subject Mice Transgenic Self Administration Mitochondrion Nucleus accumbens Pharmacology Medium spiny neuron Energy homeostasis Nucleus Accumbens Article 03 medical and health sciences Mice 0302 clinical medicine Cocaine Dopamine Uptake Inhibitors Dopamine Neuroplasticity medicine Animals Enzyme Inhibitors media_common Quinazolinones Neuronal Plasticity Chemistry Receptors Dopamine D2 General Neuroscience Addiction Dopaminergic Neurons Receptors Dopamine D1 Mitochondria Mice Inbred C57BL 030104 developmental biology Gene Expression Regulation Conditioning Operant Mitochondrial fission 030217 neurology & neurosurgery Locomotion medicine.drug |
| Zdroj: | Neuron. 96(6) |
| ISSN: | 1097-4199 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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