Modulation of endothelial and neuronal nitric oxide synthases during learning of an operant conditioning task.

Nitric oxide (NO) promotes plasticity and it is essential for learning, the NO synthases involved in these events are the endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS) isoforms. The aim of this study was to study transcription, protein expression and enzymatic activity of eNOS and nNOS in the prefrontal cortex and the hippocampus during learning an operant conditioning task. Animals were considered incompletely trained (IT) when performed between 50% and 65% of responses, whereas animals were considered trained when reached 100% of responses with a latency time lower than 5 s. Following training session animals were killed and we quantified mRNA levels by Real Time RT-PCR, protein expression by western blot and enzymatic activity. eNOS and nNOS mRNA levels were only incremented in IT group. On the contrary, protein expression of both isoforms were augmented during all learning process. Moreover, we also found that eNOS and nNOS synthase activity were incremented in IT group and in trained group. Here, we showed that during learning there is a differential regulation of eNOS and nNOS in the prefrontal cortex and hippocampus and that NO could be acting as a promoter of plasticity.