Casein kinase 1 enables nucleus accumbens amphetamine-induced locomotion by regulating AMPA receptor phosphorylation.

ABSTRACT: The closely related δ and ε isoforms of the serine/threonine protein kinase casein kinase 1 (Csnk1) have been implicated in the generation of psychostimulant-induced behaviors. In this study, we show that Csnk1δ/ε produces its effects on behavior by acting on the Darpp-32-PP1 signaling pathway to regulate AMPA receptor phosphorylation in the nucleus accumbens (NAcc). Inhibiting Csnk1δ/ε in the NAcc with the selective inhibitor PF-670462 blocks amphetamine induced locomotion and its ability to increase phosphorylation of Darpp-32 at S137 and T34, decrease PP1 activity and increase phosphorylation of the AMPA receptor subunit at S845. Consistent with these findings, preventing GluR1 phosphorylation with the alanine mutant GluR1(S845A) reduces glutamate-evoked currents in cultured medium spin

SUBMITTER: Li D 

PROVIDER: S-EPMC3129449 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature