Involvement of nitric oxide in neuroadaptations underlyind cocaine sensitization

GABACH, LAURA A; PEREZ, MARIELA F

Montevideo

Simposio; Simposio Neuron-Glia interaction in health and disease: from basic biology to translational neuroscience. Second edition; 2014

Behavioral sensitization is known as the increased sensitivity to locomotor stimulating effect after repeated psychostimulants administration, and it is believed to be relevant to drug addiction and craving in humans. It has been shown that repeated cocaine administration induces behavioral sensitization in a ¡Ö50% of treated animals. Nitric oxide could be involved in the acquisition and maintenance of behavioral effects of cocaine, probably by activation of nNOS/NO/GC/cGMP signaling pathway. Inhibition of the enzyme nNOS attenuates development of sensitization in rats, while 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 of illicit drugs in humans. By usurping normal learning mechanisms, cocaine and other drugs of abuse, reinforces compulsive behaviors that underlie addiction. Hippocampus is an important brain region for some learningprocesses,andcocainecanmodulatesynapticplasticityinthisstructure. AIM: We attempted to: 1) evaluate the impact of the nNOS/NO/GC/cGMP signaling pathway in the development of behavioral sensitization and possible changes in nNOS expression and function, 2) determine if nNOS inhibition can prevent expression of cocainesensitizationandthe associatedhippocampalsynapticplasticity.