Proteasome phosphorylation regulates cocaine-induced sensitization

Howell and Gonzales et al. show that the phosphorylation of the 26S proteasome, specifically on the Rpt6 ATPase subunit at serine 120 (S120), to be important for cocaine-induced behavioral plasticity. Cocaine increases Rpt6 S120 phosphorylation and proteasome activity in cultured neurons and in various brain regions of wild type mice including the nucleus accumbens and prefrontal cortex but not in Rpt6 S120D mutant mice in which cocaine-induced locomotor sensitization was completely absent.88