ACCIONES INHIBIDORAS DEL SILDENAFIL SOBRE EL TRANSPORTADOR DE MONOAMINA DAT PRODUCE MEJORAS EN LA PLASTICIDAD SINÁPTICA DEL HIPOCAMPO Y EFECTOS DUALES EN LA MEMORIA EN RATAS JÓVENES.

Córdoba Capital

Congreso; 1er Congreso Mundial de Toxicología, Salud Ambiental y Emergencia en Salud; 2023

The phosphodiesterase 5 inhibitor sildenafil-SILD is used for peripheral pathologies. Although, at central nervous system improves hippocampal-HP synaptic plasticity and dopamine-DA neurotransmission. Increases in DA-signaling may either interfere or improve memory formation in animal models. Aims: 1-to evaluate SILD effects in HP-dependent memories; 2-to determine if memory deficits are DA dependent; 3-to assess the SILD effects in monoamine transporter DAT function in HP and Nucleus Accumbens-NAc. Methods: male Wistar rats (50-55 days-old) received a SILD dose (5 mg/kg, ip) 2h before one of the following the behavioral tests: novel object recognition-NOR, fear conditioning-FC and step-down-SD. Another group received FAUC365 (2,5 mg/kg, sc), a D3 receptor antagonist, after SILD administration and 20 min before NOR training. HP and NAc were extracted to evaluate the DAT function. Results: SILD reduced the discrimination index in NOR, effect that was prevented by FAUC365 (Two-way ANOVA, p <0,005) and increased the freezing percentage and latency to step-down after FC and SD respectively (ANOVA, p <0,05). Furthermore, SILD reduced DAT functioning. Conclusion: SILD differentially contribute to HP-dependent memory formation influencing DA transmission, probably by reducing the DAT function and raising DA levels and transmission. In fact, in a non-aversive environment (NOR) the D3 antagonism completely reverse deficits observed, indicating that DA overload blunted normal NOR performance. Oppositely, in aversive ones (FC and SD) DA increments improved memory. These differences may account on the nature of the environmental stimuli and brain structures involved in the information processing, revealing the importance to consider central effects when using SILD.