Archival ReportWithdrawal From Cocaine Self-administration Alters the Regulation of Protein Translation in the Nucleus Accumbens
Section snippets
Subjects and Drug Self-administration
All procedures were approved by the Rosalind Franklin University Institutional Animal Care and Use Committee in accordance with the U.S. Public Health Service Guide for Care and Use of Laboratory Animals. Adult male Sprague Dawley rats underwent extended-access cocaine or saline self-administration (6 hours/day), as described previously (12) and in the Supplement.
Metabolic Labeling
Procedures were adapted from well-established protocols 22, 24 (see Supplemental Figure S1 for timeline). Rats were decapitated, and
Measuring Protein Translation in the NAc
To confirm that 35S-Met/Cys incorporates into newly translated proteins in the NAc, we preexposed tissue from naïve animals to the translation inhibitor cycloheximide (60 μM) for 30 minutes before moving the tissue into a chamber containing cycloheximide and 35S-Met/Cys for an additional 60 minutes. We then processed tissue for sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)/autoradiography. Figure 1A, B shows incorporation of 35S-Met/Cys into newly synthesized proteins
Discussion
This study is the first to characterize regulation of protein translation in the NAc by glutamate transmission. In addition, we tested the hypothesis that this regulation was altered after incubation of cocaine craving. Our results reveal mGlu5 and NMDAR regulation of translation under control conditions, loss of NMDAR regulation of translation after incubation, and increased GluA1 translation after incubation.
We suggest that our results primarily reflect translation in MSNs given that these
Acknowledgments and Disclosures
This research was supported by United States Public Health Service Grant DA015835 (to MEW), postdoctoral National Research Service Award DA040414 (to MTS), and predoctoral National Research Service Award DA036950 (to CTW).
We thank Emily Osterweil for generously sharing protocols and otherwise advising us on the metabolic labeling experiments and thank Xuan (Anna) Li for helping with the design of quantitative polymerase chain reaction experiments.
The authors report no biomedical financial
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