Phosphodiesterase 1B Knock-out Mice Exhibit Exaggerated Locomotor Hyperactivity and DARPP-32 Phosphorylation in Response to Dopamine Agonists and Display Impaired Spatial Learning

Overview

Journal J Neurosci

Specialty Neurology

Date 2002 Jun 22

PMID 12077213

Citations 38

Authors

Tracy M Reed

David R Repaske

Gretchen L Snyder

Paul Greengard

Charles V Vorhees

Affiliations

Soon will be listed here.

Abstract

Using homologous recombination, we generated mice lacking phosphodiesterase-mediated (PDE1B) cyclic nucleotide-hydrolyzing activity. PDE1B(-/-) mice showed exaggerated hyperactivity after acute D-methamphetamine administration. Striatal slices from PDE1B(-/-) mice exhibited increased levels of phospho-Thr34 DARPP-32 and phospho-Ser845 GluR1 after dopamine D1 receptor agonist or forskolin stimulation. PDE1B(-/-) and PDE1B(+/-) mice demonstrated Morris maze spatial-learning deficits. These results indicate that enhancement of cyclic nucleotide signaling by inactivation of PDE1B-mediated cyclic nucleotide hydrolysis plays a significant role in dopaminergic function through the DARPP-32 and related transduction pathways.

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