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Generalization of Contextual Fear Depends on the Activity of the Serotonin System of the Medial Prefrontal Cortex

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The medial prefrontal cortex (mPFC) is involved in regulating fear generalization. We have previously shown that the formation of generalized fear in response to sound signals is controlled by the serotonin system of the mPFC, as its pharmacological activation during acquisition of a conditioned fear reflex (CFR – a model of fear) increases at the stage of testing the manifestation of fear induced by safe sound stimuli. The aim of the present work was to determine whether the serotonin system of the mPFC is involved in the process of fear generalization. Studies in Sprague–Dawley rats using vital intracranial microdialysis showed that placing animals in potentially dangerous box A, in which they had previously acquired a CFR (a conditioned signal combined with unavoidable electrocutaneous shock), was accompanied by an increase in the extracellular serotonin level in the mPFC and induced freezing of the animals (an indicator of contextual fear). Placing the same animals in safe differential box B also led to an increase in the extracellular serotonin level in the mPFC and induced freezing of the animals (an indicator of generalized contextual fear). Administration of fluoxetine (1 μM), a selective serotonin reuptake inhibitor, into the mPFC during CFR acquisition increased freezing of the animals in safe box B at the test stage but did not affect freezing in box A. This pharmacological intervention did not alter the magnitude of increases in extracellular serotonin levels in the mPFC induced by being in boxes A or B. These data provide evidence that activation of the serotonin system of the mPFC during the formation of fear influences the extent of contextual fear generalization. In addition, our results suggest that increases in mPFC serotonin system activity by safe contextual stimuli may be among the neurochemical manifestations of generalized contextual fear.

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  1. Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg, Russia

    N. B. Saulskaya & O. E. Marchuk

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  1. N. B. Saulskaya
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Correspondence to N. B. Saulskaya.

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Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 106, No. 12, pp. 1541–1552, December, 2020.

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Saulskaya, N.B., Marchuk, O.E. Generalization of Contextual Fear Depends on the Activity of the Serotonin System of the Medial Prefrontal Cortex. Neurosci Behav Physi 51, 954–959 (2021). https://doi.org/10.1007/s11055-021-01152-9

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