Генерализация страха обстановки зависит от активности серотониновой системы медиальной префронтальной коры

Abstract

The medial prefrontal cortex (mPFC) is involved in the regulation of fear generalization. We have previously shown that generalized fear formation to auditory cues is under the control of the mPFC serotonin system, as its pharmacological activation during a conditioned fear response acquisition (CFR - a fear model) enhances fear expression to safe auditory stimuli during testing. The aim of this work was to find out whether the mPFC serotonin system is involved in the contextual fear generalization. Using in vivo intracranial microdialysis in Sprague-Dawley rats, it was shown that placing animals in a potentially dangerous box A, in which they had previously acquired CFR (the paired presentation of a conditioned cue and inescapable footshock) was accompanied by an increase in the mPFC extracellular serotonin level and caused animals animals' freezing (a contextual fear measure). Placing the same animals in a safe differentiation box B also led to the extracellular serotonin level rise in the mPFC and caused animals' freezing (a measure of contextual fear generalization). The intra-mPFC infusion of a selective serotonin reuptake inhibitor fluoxetine (1 μM) during the fear response elaboration enhanced, during testing, animals' freezing in differentiation box B but did not affect animals' freezing in box A. The fluoxetine administration during training did not change the testing-induced extracellular serotonin levels rise in the mPFC in boxes A and B. The data indicate that activation of the mPFC serotonin system during fear formation affects the degree of contextual fear generalization. In addition, they suggest that one of the neurochemical manifestations of contextual fear generalization may be an increased activity of the mPFC serotonin system in the safe environment.