Priority CommunicationA Role for Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1α in Nucleus Accumbens Neuron Subtypes in Cocaine Action
Section snippets
Animals
D1-Cre hemizygote (line FK150) or D2-Cre hemizygote (line ER44) bacterial artificial chromosome (BAC) transgenic mice from GENSAT (32, 33) (www.gensat.org) on a C57BL/6J background were used for behavioral experiments and virus validation. Homozygous RiboTag (RT) mice on a C57BL/6J background, expressing a Cre-inducible HA-Rpl22 (34), were crossed to D1-Cre or D2-Cre mouse lines to generate D1-Cre-RT and D2-Cre-RT mice (25) and used for cell type–specific ribosome-associated mRNA isolation.
Results
To determine if repeated cocaine alters PGC-1α, we first examined PGC-1α mRNA in NAc of C57BL/6J mice receiving cocaine (20 mg/kg/day for 7 days) or saline. Tissue was collected 24 hours after the last injection (Figure 1A), a time point shown to induce transcriptional and cellular plasticity in NAc (20, 25, 27, 37). Quantitative RT-PCR shows that the PGC-1a mRNA is increased in NAc after repeated cocaine (Figure 1B). We further observed an increase in PGC-1α protein in NAc after repeated
Discussion
Our data demonstrate for the first time a role for the transcriptional coactivator PGC-1α in NAc in cocaine action. Repeated cocaine exposure increases PGC-1α mRNA and protein in NAc. This increase is specific to NAc D1-MSNs because we observed an increase in PGC-1α ribosome-associated mRNA, which likely represents mRNA undergoing translation to protein in D1-MSNs after repeated cocaine. The increase in PGC-1α is consistent with enrichment of H3K4me3, a transcriptional activating methylation
Acknowledgments and Disclosures
This work is supported by National Institutes of Health Grant No. R01DA038613 (to MKL), the Brain and Behavior Research Foundation (National Association for Research on Schizophrenia and Depression Young Investigator, P&S Fund) (RC), and the Mission Interministérielle de Lutte contre les Drogues Et les Conduites Addictives (ME).
We thank Dr. K. Chandrasekharan for providing the PGC-1α vector.
All authors report no biomedical financial interests or potential conflicts of interest.
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