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

摘要

In vivo intracerebral microdialysis/HPLC studies on Sprague–Dawley rats showed that acquisition of a conditioned refl ex 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 N~ω-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 fi rst evidence that the formation of a conditioned refl ex fear reaction is accompanied by activation of the nitrergic system of the medial prefrontal cortex, refl ected in the extent of subsequent generalization but not expression of this conditioned refl ex reaction.