Withdrawal From Cocaine Self-administration Alters the Regulation of Protein Translation in the Nucleus Accumbens.
Withdrawal From Cocaine Self-administration Alters the Regulation of Protein Translation in the Nucleus Accumbens.
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DOI：
10.1016/j.biopsych.2018.02.012
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发表时间：
2018-08-01
影响因子：
10.6
通讯作者：
Wolf ME
中科院分区：
文献类型：
--
作者：
Stefanik MT;Milovanovic M;Werner CT;Spainhour JCG;Wolf ME
Cue-induced cocaine craving “incubates” during abstinence from cocaine self-administration. Expression of incubation ultimately depends upon elevation of homomeric GluA1 AMPA receptors (AMPARs) in the nucleus accumbens (NAc). This adaptation requires ongoing protein translation for its maintenance. Aberrant translation is implicated in CNS diseases, but nothing is known about glutamatergic regulation of translation in the drug-naïve NAc or after incubation. NAc tissue was obtained from drug-naïve rats and after 1 or >40 days of abstinence from extended-access cocaine or saline self-administration. Newly translated proteins were labeled using 35S-Met/Cys or puromycin. We compared basal overall translation and its regulation by mGlu1, mGlu5 and NMDA receptors (NMDARs) in naïve, saline and cocaine rats, and compared GluA1 and GluA2 translation by immunoprecipitating puromycin-labeled proteins. In all groups, overall translation was unaltered by mGlu1 blockade (LY367385) but increased by mGlu5 blockade (MTEP). NMDAR blockade (APV) increased overall translation in naïve and saline, but not cocaine, rats. Cocaine/late withdrawal rats exhibited greater translation of GluA1 (but not GluA2), which was not further affected by NMDAR blockade. Our results suggest that increased GluA1 translation contributes to the elevated homomeric GluA1 AMPAR levels in NAc that mediate incubation. Additional contributions to incubation-related plasticity may result from loss of the braking influence on translation normally exerted by NMDARs. Apart from elucidating incubation-related adaptations, we found a suppressive effect of mGlu5 on NAc translation regardless of drug exposure, which is opposite to results obtained in hippocampus and points to heterogeneity of translational regulation between brain regions.
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