Posible participation of the NO/GMPc signaling pathway in the development of cocaine sensitization

GABACH, LAURA A; MONTI, MARIA CAROLINA; RAMIREZ, OSCAR ; PÉREZ MARIELA F

Mendoza

Congreso; V Neurotoxicity Society Meeting.; 2011

Cocaine (COC) sensitization is associated to nitric oxide syntase activity and enhancement of hippocampal synaptic plasticity (HSP). We can hypothethize that the NO/cGMP signaling pathway in the brain can initiate, contribute or exacerbate addictive behaviors, being PDE5 and GMPc inhibitors potential candidates for these actions for them selfs or when they are used concomitantly with other drugs. In the present work, we treated two groups of rats: One with  the PDE5 inhibitor, sildenafil, before COC, and the other group with a specific sGC (soluble guanylate cyclase) inhibitor, ODQ (1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one),  before COC along 5 days, in order to examine the impact of the inhibition of this two enzymes in the development of COC sensitization and the associated HSP. Our results indicate that sildenafil enhances HSP and when it is co-administered with COC increases the percentage of sensitized rats, being this increase correlated to an enhanced HSP. In addition, preliminar results indicate that ODQ decreased the percentage of sensitized rats, and the correlated HSP. These findings suggest that NO/cGMP signalling pathway could be important in the development of COC sensitization and in the changes induced by COC on HSP that may contribute to the behavioral effects after repeated administration of this drug.   Financial support: MINCyT PID 100; SECYT 2010-2011 and CONICET