Neurochemistry and Neuropharmacology
Author: Maria Florencia Constantin | Email: mafconstantin@unc.edu.ar
Maria Florencia Constantin1°, Leonardo Bravo2°, Aida Marcotti1°, María Dolores Rubianes2°, Mariela Fernanda Pérez1°
1° Departamento de Farmacología Otto Orsingher, IFEC-CONICET, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba
2° Departamento de Físicoquímica, INFIQC-CONICET, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba
Sildenafil-SILD is used for the treatment of peripheral pathologies and it is also misused. In the CNS, SILD improves synaptic plasticity in hippocampus-HP and dopamine-DA neurotransmission. Increased DA signaling may either interfere with or enhance memory formation. Aims: To evaluate SILD effects in HP-dependent memories; to determine if memory deficits are DA-dependent; and to assess SILD effects on re-uptake kinetics of monoamine transporter DAT in HP and nucleus accumbens-NAc. Methods: male Wistar rats (50 days old) received an acute (P1) or a daily SILD dose for 10 days (P2) starting behavioral tests 2h or 24h after the last dose, respectively. Tests included novel object recognition-NOR and fear conditioning-FC. Another P1 group received FAUC365 (D3 antagonist) 20 min before NOR training. HP and NAc were extracted after P1 to evaluate the DAT function. Results: SILD reduced the discrimination index in NOR, which was prevented by FAUC365 after P1, and increased the freezing % after FC. SILD also reduced DA reuptake after P1 in HP and NAc. Conclusion: SILD differentially affected HP-dependent memory formation, possibly by increasing DA transmission through DAT inhibition. D3 antagonism reversed NOR deficits, suggesting DA overload impaired normal NOR performance. In an aversive environment, DA increments improved memory. This suggests SILD may negatively affect young, healthy subjects, highlighting the importance of considering central effects when using SILD.