It has been shown that repeated cocaine administration induces behavioral sensitization in a ¡Ö 50 % of treated animals. Nitric oxide could be involved in the acquisition and maintenance of behavioral effects of cocaine, probably by activation of GC/cGMP signaling pathway, since inhibition of the enzyme Nitric Oxide Synthase attenuates the development of sensitization. Repeated cocaine administration induced an increase in hippocampal synaptic plasticity, which is more pronounced in cocaine sensitized rats.
PDE5 is a cGMP-specific enzyme, that is expressed in hippocampus, hydrolyzes cGMP, being cGMP one of the targets for the action of nitric oxide. It has been reported the misuse and recreational use of PDE5 inhibitors, such as sildenafil, and also the concomitant use with illicit drugs has been described in humans.
HYPOTHESIS: Engagement of the NO/cGMP signaling pathways in the brain can initiate, contribute or exacerbate addictive behaviors in humans, being inhibitors of PDE5 potential candidates for these actions.
AIM: Examine the impact of the inhibition of the degradation of cGMP in the development of behavioral sensitization and the associated synaptic plasticity.
