Activity of the Nitrergic System of the Medial Prefrontal Cortex in Rats with High and Low Levels of Generalization of a Conditioned Reflex Fear Reaction

In vivo intracerebral microdialysis/HPLC studies on Sprague–Dawley rats showed that acquisition of a conditioned reflex fear reaction (combined conditioned sound stimulus and unavoidable electrocutaneous shock) was accompanied by an increase in the level of extracellular citrulline (a coproduct of NO synthesis) in the medial area of the prefrontal cortex. This increase was almost completely blocked by administration of the neuronal NO synthase inhibitor Nω-propyl-L-arginine (1 mM) into this area of the cortex and was not seen in animals of the control group. These increases were large in animals subsequently showing low levels of freezing (a measure of fear) in response to the differential signal not previously combined with the pain stimulus and low in rats with high levels of freezing in response to the differential signal, though they did not correlate with the level of freezing in response to the conditioned signal. These data provide the first evidence that the formation of a conditioned reflex fear reaction is accompanied by activation of the nitrergic system of the medial prefrontal cortex, reflected in the extent of subsequent generalization but not expression of this conditioned reflex reaction. © 2016, Springer Science+Business Media New York.