Neuron (Cambridge, Mass.), 2017-12, Vol.96 (6), p.1327-1341.e6
- Chandra, Ramesh
- Engeln, Michel
- Schiefer, Christopher
- Patton, Mary H.
- Martin, Jennifer A.
- Werner, Craig T.
- Riggs, Lace M.
- Francis, T. Chase
- McGlincy, Madeleine
- Evans, Brianna
- Nam, Hyungwoo
- Das, Shweta
- Girven, Kasey
- Konkalmatt, Prasad
- Gancarz, Amy M.
- Golden, Sam A.
- Iñiguez, Sergio D.
- Russo, Scott J.
- Turecki, Gustavo
- Mathur, Brian N.
- Creed, Meaghan
- Dietz, David M.
- Lobo, Mary Kay
2017
Details
- Autor(en) / Beteiligte
- Chandra, Ramesh
- Engeln, Michel
- Schiefer, Christopher
- Patton, Mary H.
- Martin, Jennifer A.
- Werner, Craig T.
- Riggs, Lace M.
- Francis, T. Chase
- McGlincy, Madeleine
- Evans, Brianna
- Nam, Hyungwoo
- Das, Shweta
- Girven, Kasey
- Konkalmatt, Prasad
- Gancarz, Amy M.
- Golden, Sam A.
- Iñiguez, Sergio D.
- Russo, Scott J.
- Turecki, Gustavo
- Mathur, Brian N.
- Creed, Meaghan
- Dietz, David M.
- Lobo, Mary Kay
- Titel
- Drp1 Mitochondrial Fission in D1 Neurons Mediates Behavioral and Cellular Plasticity during Early Cocaine Abstinence
- Ist Teil von
- Neuron (Cambridge, Mass.), 2017-12, Vol.96 (6), p.1327-1341.e6
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2017
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. •Cocaine promotes mitochondrial fission in NAc D1-MSNs through Drp1 activation•Mdivi-1 blunts drug-induced behaviors and excitatory synaptic function in D1-MSNs•NAc D1-MSN genetic reduction of Drp1 blunts drug seeking after early abstinence•Enhancing fission in D1-MSNs potentiates drug seeking after long-term abstinence Chandra, Engeln et al. show that mitochondrial division and its molecular mediator, Drp1, are increased in nucleus accumbens D1-MSNs after repeated cocaine. Pharmacological or genetic blockade of mitochondrial division prevents physiological and behavioral outcomes to cocaine during early drug abstinence.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0896-6273eISSN: 1097-4199DOI: 10.1016/j.neuron.2017.11.037Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5747376
- Format
- –
- Schlagworte
- Addiction, Animals, Behavior, Behavioral plasticity, Brain, c-Fos protein, Cocaine, Cocaine - administration & dosage, Cocaine - pharmacology, Conditioning, Operant - drug effects, Conditioning, Operant - physiology, Dendrites, Dopamine, Dopamine D1 receptors, Dopamine Uptake Inhibitors - administration & dosage, Dopamine Uptake Inhibitors - pharmacology, Dopaminergic Neurons - drug effects, Dopaminergic Neurons - ultrastructure, Drp1, Drug abuse, Drug self-administration, Dynamin, Dynamins - genetics, Dynamins - metabolism, Energy balance, Enzyme Inhibitors - pharmacology, Fission, Fos protein, Gene expression, Gene Expression Regulation - drug effects, Gene Expression Regulation - genetics, Homeostasis, Locomotion - drug effects, Locomotion - genetics, medium spiny neurons, Metabolism, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mitochondria, Mitochondria - drug effects, Mitochondria - metabolism, Mitochondrial DNA, Narcotics, Neuronal Plasticity - drug effects, Neuronal Plasticity - genetics, Neurons, Nucleus accumbens, Nucleus Accumbens - cytology, Plastic foam, Proteins, Quinazolinones - pharmacology, Receptors, Dopamine D1 - genetics, Receptors, Dopamine D1 - metabolism, Receptors, Dopamine D2 - genetics, Receptors, Dopamine D2 - metabolism, Respiration, Rodents, Self Administration, Spiny neurons, Studies