INHIBITION OF SEROTONIN REUPTAKE IN THE MEDIAL PREFRONTAL CORTEX DURING CONDITIONED FEAR RESPONSE ELABORATION PROMOTES GENERALIZED FEAR FORMATION

In Sprague-Dawley rats by means of in vivo microdialysis it was shown that an acquisition of a conditioned fear response (the paired presentation of an auditory conditioned cue (CS+) and inescapable footshock) was accompanied by an extracellular serotonin level rise in the medial prefrontal cortex. The infusion of 104 fluoxetine, a selective serotonin reuptake inhibitor, into the medial prefrontal cortex during the conditioned fear response acquisition, at first, increased the serotonin rise observed in this brain area during the acquisition. Secondly, the fluoxetine infusion enhanced, a day after it, animals' freezing (a fear measure) to a differential cue (CS-) that was not associated with footshock (a fear generalization test), but did not affect freezing to CS+, previously paired with footshock (a fear expression test). The data obtained indicate for the first time that the serotonergic stimulation of the medial prefrontal cortex during the elaboration of the conditioned fear response promotes future generalization of fear response but does not affect fear response acquisition.