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

@article{citeulike:3008946, abstract = {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.}, address = {Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Ave., New York, New York 10065, USA.}, author = {Bateup, Helen S S. and Svenningsson, Per and Kuroiwa, Mahomi and Gong, Shiaoching and Nishi, Akinori and Heintz, Nathaniel and Greengard, Paul }, citeulike-article-id = {3008946}, doi = {10.1038/nn.2153}, issn = {1097-6256}, journal = {Nature neuroscience}, month = {July}, posted-at = {2008-07-16 17:49:12}, priority = {2}, title = {Cell type-specific regulation of DARPP-32 phosphorylation by psychostimulant and antipsychotic drugs.}, url = {http://dx.doi.org/10.1038/nn.2153}, year = {2008} }

TY - JOUR ID - citeulike:3008946 L3 - citeulike-article-id:3008946 TI - Cell type-specific regulation of DARPP-32 phosphorylation by psychostimulant and antipsychotic drugs. JF - Nature neuroscience AD - Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Ave., New York, New York 10065, USA. SN - 1097-6256 N2 - 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. AU - Bateup, Helen S AU - Svenningsson, Per AU - Kuroiwa, Mahomi AU - Gong, Shiaoching AU - Nishi, Akinori AU - Heintz, Nathaniel AU - Greengard, Paul PY - 2008/07/11/ UR - http://dx.doi.org/10.1038/nn.2153 ER -