The Alterations in Mitochondrial DNA Copy Number and Nuclear-Encoded Mitochondrial Genes in Rat Brain Structures after Cocaine Self-Administration.
The repeated intake of cocaine evokes oxidative stress that is present even during drug withdrawal. Recent studies demonstrate that cocaine-induced oxidative and/or endoplasmic reticulum stress can affect mitochondrial function and dynamics as well as the expression of mitochondrial and nuclear genes. These alterations in mitochondrial function may determine synaptic and behavioral plasticity. Mitochondria and mitochondrial DNA (mtDNA) seem to play an important role in the initiation of drug addiction. We used a microarray approach to investigate the expression patterns of nuclear-encoded genes relevant for mitochondrial functions and quantitative real-time PCR assays to determine the numbers of copies of mtDNA and of mRNAs corresponding to two mitochondrial proteins in the prefrontal cortex and hippocampus of rats during early cocaine abstinence. We found a significant elevation in the copy number of mtDNA and concomitant increased expression of mitochondrial genes. Moreover, microarray analysis revealed changes in the transcription of nuclear genes engaged in mtDNA replication, nucleoid formation, the oxidative phosphorylation pathway, and mitochondrial fission and fusion. Finally, we observed the upregulation of endoplasmic reticulum stress-induced genes. Cocaine self-administration influences the expression of both nuclear and mitochondrial genes as well as mtDNA replication. To determine whether these alterations serve as compensatory mechanisms to help maintain normal level of ATP production, further studies are necessary.
Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology Polish Academy of Science, Smetna 12, 31-343, Krakow, Poland. annasc@if-pan.krakow.pl.
Anna
A
Sadakierska-Chudy
Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology Polish Academy of Science, Smetna 12, 31-343, Krakow, Poland.|Faculty of Biology and Earth Science, Neurobiology, Jagiellonian University, Krakow, Poland.
Agnieszka
A
Kotarska
Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology Polish Academy of Science, Smetna 12, 31-343, Krakow, Poland.
Małgorzata
M
Frankowska
Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology Polish Academy of Science, Smetna 12, 31-343, Krakow, Poland.
Joanna
J
Jastrzębska
Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology Polish Academy of Science, Smetna 12, 31-343, Krakow, Poland.
Karolina
K
Wydra
Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology Polish Academy of Science, Smetna 12, 31-343, Krakow, Poland.
Joanna
J
Miszkiel
Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology Polish Academy of Science, Smetna 12, 31-343, Krakow, Poland.
Edmund
E
Przegaliński
Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology Polish Academy of Science, Smetna 12, 31-343, Krakow, Poland.
Małgorzata
M
Filip
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D056915:DNA Copy Number Variations / Q000187:drug effects / Q000502:physiology*; D050259:Genes, Mitochondrial / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration
D003042:Cocaine
Cocaine self-administration; Gene expression; Microarray; Mitochondrial dynamics; Oxidative stress; mtDNA copy number