| First Author | Reed TM | Year | 2002 |
| Journal | J Neurosci | Volume | 22 |
| Issue | 12 | Pages | 5188-97 |
| PubMed ID | 12077213 | Mgi Jnum | J:77514 |
| Mgi Id | MGI:2181913 | Doi | 10.1523/JNEUROSCI.22-12-05188.2002 |
| Citation | Reed TM, et al. (2002) Phosphodiesterase 1B knock-out mice exhibit exaggerated locomotor hyperactivity and DARPP-32 phosphorylation in response to dopamine agonists and display impaired spatial learning. J Neurosci 22(12):5188-97 |
| abstractText | 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. |
