{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:15:59Z","timestamp":1791198959513,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2006,3,28]],"date-time":"2006-03-28T00:00:00Z","timestamp":1143504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Brain and Behavior"],"published-print":{"date-parts":[[2006,10]]},"abstract":"<jats:p> <jats:bold>Mice lacking phosphodiesterase 1B (PDE1B) exhibit an exaggerated locomotor response to <jats:sc>d<\/jats:sc>\u2010methamphetamine and increased <jats:italic>in vitro<\/jats:italic> phosphorylation of DARPP32 (dopamine\u2010 and cAMP\u2010regulated phosphoprotein, M<jats:sub>r<\/jats:sub> 32\u2003kDa) at Thr<jats:sup>34<\/jats:sup> in striatal brain slices treated with the D1 receptor agonist, SKF81297. These results indicated a possible regulatory role for PDE1B in pathways involving DARPP32. Here, we generated <jats:italic>PDE1B<\/jats:italic>\u2003\u00d7\u2003<jats:italic>DARPP32<\/jats:italic> double\u2010knockout (double\u2010KO) mice to test the role of PDE1B in DARPP32\u2010dependent pathways <jats:italic>in vivo<\/jats:italic>. Analysis of the response to <jats:sc>d<\/jats:sc>\u2010methamphetamine on locomotor activity showed that the hyperactivity experienced by PDE1B mutant mice was blocked in <jats:italic>PDE1B<\/jats:italic><jats:sup><jats:italic>\u2013\/\u2013<\/jats:italic><\/jats:sup><jats:italic>x DARPP32<\/jats:italic><jats:sup><jats:italic>\u2013\/\u2013<\/jats:italic><\/jats:sup> double\u2010KO mice, consistent with participation of PDE1B and DARPP32 in the same pathway. Further behavioral testing in the elevated zero\u2010maze revealed that <jats:italic>DARPP32<\/jats:italic><jats:sup><jats:italic>\u2013\/\u2013<\/jats:italic><\/jats:sup> mice showed a less anxious phenotype that was nullified in double\u2010mutant mice. In contrast, in the Morris water maze, double\u2010KO mice showed deficits in spatial reversal learning not observed in either single mutant compared with wild\u2010type mice. The data suggest a role for PDE1B in locomotor responses to psychostimulants through modulation of DARPP32\u2010dependent pathways; however, this modulation does not necessarily impact other behaviors, such as anxiety or learning. Instead, the phenotype of double\u2010KOs observed in these latter tasks may be mediated through independent pathways.<\/jats:bold> <\/jats:p>","DOI":"10.1111\/j.1601-183x.2006.00209.x","type":"journal-article","created":{"date-parts":[[2006,3,28]],"date-time":"2006-03-28T09:22:49Z","timestamp":1143537769000},"page":"540-551","source":"Crossref","is-referenced-by-count":45,"title":["Phosphodiesterase 1B differentially modulates the effects of methamphetamine on locomotor activity and spatial learning through DARPP32\u2010dependent pathways: evidence from PDE1B\u2010DARPP32 double\u2010knockout mice"],"prefix":"10.1111","volume":"5","author":[{"given":"L. A.","family":"Ehrman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. T.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. 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