D1 receptor modulation of memory retrieval performance is associated with changes in pCREB and pDARPP-32 in rat prefrontal cortex

We have recently shown a significant role of dopamine D1 receptors in recognition and temporal order memory retrieval for objects in rodents [Hotte M, Naudon L, Jay TM. Modulation of recognition and temporal order memory retrieval by dopamine D(1) receptor in rats. Neurobiol Learn Mem 2005;84:85–92]. The present study investigates the signal transduction pathways underlying dopamine D1 receptor modulation of retrieval performance in these memory tasks at different delays. We analyzed the level of phosphorylation of both CREB (cAMP response element binding protein) and DARPP-32 (dopamine and cAMP-regulated phosphoprotein, 32 kDa) in (1) the prefrontal cortex of rats that had performed the object recognition task, (2) the prefrontal and perirhinal cortices of rats that had performed the temporal order memory task for objects. For comparison, we explored the phosphorylation state of CREB and DARPP-32 in the prefrontal cortex, nucleus accumbens and hippocampus of rats having performed badly on the delayed spatial win-shift task after D1 blockade. The improvement in recognition and temporal order memory performance at a 4 h-delay was associated with an increased phosphorylation of both CREB and DARPP-32 in the prefrontal cortex of rats treated with the D1 agonist SKF 81297. By contrast, the significant impairment of delayed spatial memory retrieval after administration of the selective D1 antagonist SCH 23390 was associated with decreased phosphorylation of CREB and DARPP-32 in the prefrontal cortex. These results provide insight into molecular mechanisms involved in D1 receptor-dependent modulation of short- versus long-term memory in prefrontal cortex where DARPP-32 in synergy with CREB may represent a pivotal role.