Nitrergic Activity of the Medial Prefrontal Cortex in Rats with High and Low Conditioned Fear Generalization

For Sprague-Dawley rats by means of in vivo microdialysis combined with HPLC analysis it was shown that an acquisition of a conditioned fear response (paired presentation of an auditory conditioned stimulus (CS+) and unescapable footshock) caused the increase in extracellular levels of citrulline (an NO co-product) in the medial prefrontal cortex which was almost completely prevented by local infusions of 1 mM N omega-propil-L-arginine, a neuronal NO synthase inhibitor and was not observed in control rats. The magnitude of this increase was high in rats showing later low freezing to conditioned stimulus previously not paired with footshock (CS-) and it was low in rats characterized by high freezing to CS, but it did not interfere with freezing to the conditioned stimulus CS+ previously paired with footshock. The data obtained indicate for the first time that the conditioned fear acquisition is accompanied by nitrergic activation within the medial prefrontal cortex which is associated with conditioned fear generalization but not with conditioned fear expression.