IFEC   20925
INSTITUTO DE FARMACOLOGIA EXPERIMENTAL DE CORDOBA
Unidad Ejecutora - UE
artículos
Título:
Involvement of nNOS/NO/sGC/cGMP signaling pathway in cocaine sensitization and in the associated hippocampal alterations: Does Phosphodiesterase 5 inhibition help to drug vulnerability?
Autor/es:
LAURA GABACH; VALERIA P CARLINI; CAROLINA MONTI; LAURA MAGLIO; SUSANA RUBIALES; MARIELA F PEREZ
Revista:
PSYCHOPHARMACOLOGY
Editorial:
SPRINGER
Referencias:
Lugar: Berlin; Año: 2013 p. 41 - 50
ISSN:
0033-3158
Resumen:
Repeated cocaine administration induces behavioral sensitization in about 50 % of treated animals. Nitric oxide could be involved in the acquisition and maintenance of behavioral cocaine effects, probably by activation of nNOS/NO/sGC/cGMP signaling pathway, since inhibition of the nNOS enzyme attenuates development of sensitization in rats. On the other hand, increased cGMP availability 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 conditioning to general context previously associated to drug availability, influencing drug-seeking behavior and sensitization. Moreover, cocaine and other drugs of abuse can affect the strength of glutamate synapses in this structure, lastly modifying neuronal activity in main regions of the reward circuitry. In the present work we attempted to determine whether the pharmacological manipulation of nNOS/NO/sGC/cGMP signaling pathway altered 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.