COULD VARIATIONS IN nNOS LEVELS DRIVE EXPRESSION OF COCAINE SENSITIZATION?

GABACH LAURA; ARTUR DE LA VILLARMOIS EMILCE; GHERSI MARISA; VALERIA PAOLA CARLINI; MARIELA FERNANDA PÉREZ

Córdoba

Congreso; 3° Reunión Internacional de Ciencias Farmacéuticas - RICiFa 2014 -; 2014

Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba. Departamento de Farmacia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario

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. Repeated cocaine induces behavioral sensitization in a 50% of treated male Wistar rats and it can modulate synaptic plasticity in the hippocampus, which is an important brain region for the associative learning processes occurring during addiction. Nitric oxide is a neurotransmitter involved in a broad range of effects in the central nervous system including synaptic plasticity and complex behavioral responses among others. We have previously demonstrated a key role of nNOS/NO/sGC/cGMP signaling pathway in the development of cocaine sensitization and in the associated enhancement of hippocampal synaptic plasticity (HSP). In the present work, we attempted to determine constitutive differences in nNOS protein levels between sensitized and non-sensitized groups, and whether nNOS inhibition after sensitization reverses the behavioral effect of cocaine and the associated hippocampal synaptic plasticity. We administered five daily cocaine injections (i.p) to 35 days old Wistar rats, followed by five daily 7-nitroindazole (nNOS inhibitor) or vehicle injections (i.p). We tested development of cocaine sensitization (in vivo) and the threshold for LTP in hippocampus (in vitro) as indicator of synaptic plasticity. We observed that only sensitized rats showed significant increases in nNOS protein levels compared to non-sensitized and control groups. Furthermore, nNOS inhibition after repeated cocaine administration reversed behavioral sensitization and the highest level of hippocampal plasticity. In conclusion, we can speculate that repeated cocaine exposure has differential impact within subjects, increasing nNOS protein levels and in consequence NO in hippocampus only in sensitized animals. Then, nNOS inhibition can restore NO function in hippocampus and reverse cocaine sensitization. Moreover, changes in NO function and nNOS activity in other brain areas related to the reward system that contribute to cocaine sensitization must be considered.