Cell type-specific regulation of DARPP-32 phosphorylation by psychostimulant and antipsychotic drugs

  • Bateup H
  • Svenningsson P
  • Kuroiwa M
 et al. 
  • 147


    Mendeley users who have this article in their library.
  • 140


    Citations of this article.


DARPP-32 is a dual-function protein kinase/phosphatase inhibitor that is involved in striatal signaling. The phosphorylation of DARPP-32 at threonine 34 is essential for mediating the effects of both psychostimulant and antipsychotic drugs; however, these drugs are known to have opposing behavioral and clinical effects. We hypothesized that these drugs exert differential effects on striatonigral and striatopallidal neurons, which comprise distinct output pathways of the basal ganglia. To directly test this idea, we developed bacterial artificial chromosome transgenic mice that allowed the analysis of DARPP-32 phosphorylation selectively in striatonigral and striatopallidal neurons. Using this new methodology, we found that cocaine, a psychostimulant, and haloperidol, a sedation-producing antipsychotic, exert differential effects on DARPP-32 phosphorylation in the two neuronal populations that can explain their opposing behavioral effects. Furthermore, we found that a variety of drugs that target the striatum have cell type-specific effects that previous methods were not able to discern.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


  • Helen S. Bateup

  • Per Svenningsson

  • Mahomi Kuroiwa

  • Shiaoching Gong

  • Akinori Nishi

  • Nathaniel Heintz

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free