Activation of the dopamine D₁ receptor can extend long-term spatial memory persistence via PKA signaling in mice

Many works have been performed to understand the mechanisms of the formation and persistence of memory. However, it is not fully understood whether the decay of long-term memory can be modulated by the activation of dopamine D₁ receptor. A Barnes maze task was employed to measure long-term spatial memory. We observed that the spatial memory acquired through 3 trials per session for 4 days had begun to fade out by the 14th day and had completely disappeared by 21 days after the first probe test. The intraperitoneal administration of SKF 38393 (a dopamine D₁ receptor agonist) for 7 days beginning on the 14th day after the first probe test prevented natural memory forgetting, and the intraperitoneal administration of SCH 23390 (a dopamine D₁ receptor antagonist) prevented this memory persistence. In the Western blotting, the administration of SKF 38393 increased the phosphorylation levels of PKA, ERK1/2, CaMKII, and CREB in the hippocampus. In addition, such increased levels were decreased by the corresponding antagonist (SCH 23390). Moreover, the inhibition of PKA could completely reverse the preservation of spatial memory induced by dopamine D₁ receptor activation. These results suggest that the activation of the dopamine D₁ receptor plays a critical role in the persistence of long-term spatial memory through the PKA signaling pathway.