Could variations in nNOS levels drive expression of Cocaine sensitization?

LAURA GABACH,; EMILCE ARTUR DE LA VILLARMOIS; MARISA GHERSI,; VALERIA CARLINI; MARIELA F. PEREZ

Córdoba

Congreso; RICiFa 2014; 2014

Universidad Nacional de Córdoba-Universidad Nacional de Rosario

Behavioral sensitization it is known as the increased sensitivity to locomotor stimulating effect after repeated psychostimulants administration, and 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 some 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 whether the inhibition of nNOS after sensitization reverses this behavioral effect 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) 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. The results show that inhibition of nNOS after repeated cocaine administration reversed behavioral sensitization and the highest level of plasticity induced by repeated cocaine. We also measured nNOS expression in HP and discovered that sensitized rats show and increased in nNOS expression compared to non-sensitized and control rats, indicating that the enhancement in NOS activity is due to the increase in nNOS protein levels. Therefore, considering that nNOS/NO/sGC/cGMP signaling pathway in the brain can initiate, contribute or exacerbate addictive behaviors, the interference of this pathway, even after development of cocaine sensitization, could be a useful tool to reduce susceptibility to relapse.