Inhibition of nNOS not only prevents but also reverses cocaine sensitization?

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

Congreso; XV Congreso de la Sociedad Española de Neurociencias; 2013

Repeated cocaine administration induces behavioral sensitization in about 50% of treated male Wistar rats, and modulates synaptic plasticity in the hippocampus which is an important region for some learning processes. We have demonstrated previously a key role of NO/sGC/cGMP signaling pathway in the development of cocaine sensitization and in the associated enhancement of HSP, using a protocol of concomitantly administration of cocaine and nNOS inhibitor. In the present work, we attempted to determine whether the inhibition of nNOS reverse the changes induced by repeated cocaine exposure in behavioral sensitization and the associated hippocampal synaptic plasticity (HSP). We create a new protocol using a nNOS inhibitor during 5 day after repeated cocaine exposure and evaluated locomotor activity and HSP. The results shows that inhibition of nNOS after repeated cocaine, reduced behavioral sensitization and revert the highest plasticity produced by repeated cocaine. Similar results in behavior and HSP were observed when nNOS inhibitor was administered concomitantly with repeated cocaine. Therefore we consider that nNOS/NO/sGC/cGMP signaling pathway in the brain can initiate, contribute or exacerbate addictive behaviors, and that the interference of this pathway even after sensitization to cocaine could reduce the propensity to relapse.