Temporary inactivation of the infralimbic cortex impairs while the blockade of its dopamine D2 receptors enhances auditory fear extinction in rats

Abstract

Fear extinction is defined as decline in conditioned fear responses that occurs with repeated and non-reinforced exposure to a feared conditioned stimulus. Experimental evidence suggests that the extinction of fear memory requires the integration of the medial prefrontal cortex (mPFC); nevertheless, the role of its sub-regions in regulating the expression and extinction of auditory fear has been rarely addressed in literature. The present study examined the roles of the infra-limbic (IL) and pre-limbic (PL) regions of the mPFC in the expression and extinction of auditory fear by temporally deactivating these regions using lidocaine (10 μg/0.5 μl) before training male Wistar rats in auditory fear-conditioning tasks. The results showed increased freezing levels and impaired extinction through deactivating the IL rather than the PL cortex. Given the role of the dopaminergic pathways in regulating fear memory, this study also investigated the role of D2 receptors located in the IL cortex in fear extinction. Fear extinction was improved in an inverted U-shape pattern through the intra-IL infusion of 15.125, 31.25, 62.5, 125, 250 and 500 ng/0.5 μl of the D2 receptor antagonist sulpiride. In other words, the moderate doses, i.e. 31.25, 62.5, 125, 250 ng/0.5 μl, enhanced auditory fear extinction, whereas the lowest and highest doses, i.e. 15.125 and 500 ng/0.5 μl, were ineffective. These findings demonstrated the key roles of the IL cortex and its dopamine D2 receptors in regulating auditory fear in rats.