EFFECTS OF A SINGLE SILDENAFIL EXPOSURE IN MEMORY ACQUISITION AND HIPPOCAMPAL SYNAPTIC TRANSMISSION.

EMILCE ARTUR DE LA VILLARMOIS; LAURA GABACH; CALFA G; MARIELA F. PEREZ

Rio de Janeiro

Congreso; IBRO 2015 9 World Congress; 2015

IBRO

Sildenafil (SILD) is a drug widely used in clinical practice to treat mainly erectile dysfunction by inhibition of phosphodiesterase type 5 (PDE-5) in the periphery, and the consequent increases in cGMP levels, enhancing, by crossing over, the signaling pathway activated by nitric oxide (NO/GC/GMP). SILD crosses blood brain barrier, and PDE- 5 is expressed in different brain regions. In the hipocampus NO increases glutamate release, which is essential for the long term potentiation (LTP) maintenance, a synaptic plasticity phenomenon that underlie learning and memory formation. Furthermore, it has been shown that a single SILD exposure enhances memory consolidation in a one-trial step-through inhibitory avoidance task, when administered to male mice immediately after training. Previous results from our laboratory showed a facilitation in hippocampal LTP generation 2 hours after a single SILD dose, however little is known about the persistence of those changes in hippocampus. Therefore, the aim of the present research is to evaluate the effect of SILD in memory acquisition and to characterize the persistence of the enhanced hippocampal synaptic transmition 24 hours and 7 days after SILD administration. Then, male Wistar rats were administrated with 5mg/kg (i.p) of SILD before training in the step down test and 24 hours after they were tested for memory acquisition. Immediately after the test or 7 days after, animals were sacrificed for electrophysiological experiments. Our results showed that animals administered with SILD have an increased latency time in the step down test (86,5) compared to the control group (45,0) Mann-Whitney U=51. Furthermore, a single SILD dose enhanced hippocampal synaptic plasticity, by reducing threshold to induce LTP in both, 24 hours (34,29 ± 8,123,(sild) -60,00 ± 0,0(salina)) t(10)=2,638 and 7 days (30,00 ± 5,774 (sild)- 60,00 ± 0,0, n=4(salina) t(6)=5,196 after SILD administration. These results indicate that a single SILD exposure improves memory acquisition and induced persistent changes in hippocampal synaptic plasticity that may contribute to the enhanced memory acquisition and consolidation.