Involvement of nNOS/NO/cGMP signaling pathway in cocaine sensitization and in the associated hippocampal alterations: Does Phosphodiesterase 5 inhibition help?

GABACH, LAURA A; MONTI M CAROLINA; RAMIREZ OSCAR; PEREZ, MARIELA F

Buenos Aires

Workshop; Fronteras en Biociencia; 2012

MINCyT

Repeated cocaine administration induces behavioral sensitization in a  50 % of treated animals. Nitric oxide could be involved in the acquisition and maintenance of behavioral effects of cocaine, probably by activation of nNOS/NO/sGC/cGMP signaling pathway, since inhibition of the enzyme nNOS attenuates development of sensitization in rats. On the other hand, impaired cGMP hydrolysis by Phosphodiesterase 5 inhibitors has been correlated to the misuse and recreational use of these agents, and also to the concomitant use with illicit drugs in humans. Hippocampus is an important brain region for some learning processes, and cocaine can modulate synaptic plasticity in this structure. In the present work we attempted to determine whether the pharmacological manipulation of nNOS/NO/sGC/cGMP signaling pathway altered the changes induced by repeated cocaine exposure. We demonstrate a key role of the nNOS activity and NO/sGC/cGMP signaling pathway in the development of cocaine sensitization and in the associated enhancement of hippocampal synaptic transmission.