Post-training intrahippocampal infusion of nicotine–bucladesine combination causes a synergistic enhancement effect on spatial memory retention in rats

We previously had shown that bilateral intrahippocampal infusion of 1 μg nicotine (but not 0.5 μg dose) led to an improvement in spatial memory retention in the Morris water maze task in male rats. We also reported that a similar type of bilateral infusion of H89, a protein kinase AII (PKA II) inhibitor, caused a deficit in spatial memory retention. In the present study, we wished to test the hypothesis that intrahippocampal infusion of dibutyryl cyclic AMP (DB-cAMP also called bucladesine), a membrane permeable selective activator of PKA, into the CA1 region can cause an improvement in spatial memory in this maze task. Indeed, bilateral infusion of 10 and 100 μM bucladesine (but not 1 and 5 μM doses) led to a significant reduction in escape latency and travel distance (showing an improvement in spatial memory) compared to the control. Also, bilateral infusion of 0.5 μg nicotine or 1 μM bucladesine alone did not lead to an improvement in spatial memory. However, such bilateral infusion of bucladesine at 1 and 5 μM concentrations infused within minutes after 0.5 μg nicotine infusion improved spatial memory retention. Taken together, our data suggest that intrahippocampal bucladesine infusions improve spatial memory retention in male rats and that bucladesine can interact synergistically with nicotine to improve spatial memory.