[INVOLVEMENT OF THE NITRERGIC SYSTEM OF THE PREFRONTAL CORTEX IN FEAR EXPRESSION INDUCED BY CONTEXTUAL SIGNALS OF DANGER].

In Sprague-Dawley rats by means of in vivo microdialysis, we have shown that presentation to rats a conditioned chamber in which a ton was previously paired with footshock (acquisition of a conditioned fear response to the tone) produces an increase in extracellular levels of citrulline (an NO co-product) in the medial prefrontal cortex and results in freezing response (fear index). This increase was not observed in control rats (same procedure, no footshock) and it was prevented by infusions into the medial prefrontal cortex of N®-propyl-L-arginine (1 mM), a neuronal NO synthase inhibitor. The infusion of 1mM N®-propyl-L-arginine into the medial prefrontal cortex reduced freezing to the conditioned chamber, but did not affect movement activity of the rats.

[SOUND SIGNALS OF DANGER ACTIVATE THE NITRERGIC SYSTEM OF THE MEDIAL PREFRONTAL CORTEX].

In Sprague-Dawley rats by means of in vivo microdialysis, we have shown that presentation to rats-during conditioned fear expression of a sound conditioned stimulus previously paired with footshock (CS+) produces an increase in extracellular levels of citrulline (an NO co-product) in the medial prefrontal cortex. Presentation to the same rats of a different sound stimulus (not associated with footshock) (CS-) causes a very small increase in extracellular citrulline level. CS+ induced citrulline increase is prevented by infusions into the medial prefrontal cortex of Nomega-propyl-L-arginine (1 mM), a neuronal NO synthase inhibitor and it is not observed in control rats (same procedure, no footshock).

[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 NΩ-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.

[Dopamine-NO interaction in the nucleus accumbens during stress-induced inhibition of expliratory behavior].

In Sprague-Dawley rats by means of in vivo microdialysis it was shown that stress, evoked by conditioned fear response acquisition, resulted in inhibition of exploratory behavior and produced a reduction of exploration-induced rise in extracellular levels of citrulline (an NO co-product) in the nucleus accumbens which were observed 24 hours after the stress. Intra-accumbal infusion of dopamine D2 receptor antagonist raclopride (10 μM), made after the conditioned fear response acquisition, in 24 hours after the infusion, restore the exploratory behavior and exploration-induced rise of extracellular levels of citrulline in this brain area. The data obtained indicate for the first time that stress-induced inhibition of the exploratory behavior might be mediated by inhibition of the nucleus accumbens nitrergic system occurring under the control of D2 receptors of this brain area.

Activation of the NO-ergic system of the nucleus accumbens on presentation of contextual danger signals.

Studies in Sprague-Dawley rats using intracerebral microdialysis combined with HPLC showed that presentation of the animals with a chamber in which they had previously acquired a conditioned reflex fear reaction (combination of a tone and electric shocks) led to increases in extracellular citrulline (a co-product of NO synthesis) in the medial segment of the nucleus accumbens. This increase was prevented by local administration of the NO synthase inhibitor 7-nitroindazole (0.5 mM).