Comparison of the Effects of Deep Brain Stimulation of the Prelimbic Cortex and Basolateral Amygdala for Facilitation of Extinction Process of Conditioned Fear

Abstract

Background: The study of the biological basis of fear in animal models has progressed considerably because of the energy and space that the brain devotes to this basic emotion. Electrical stimulation targets several structures of the brain to examine its behavioral effects and to understand the role of different regions in underlying mechanisms of fear processing and anxiety in preclinical models. Objectives: In this study, the effects of high-frequency deep brain stimulation (DBS) of the basolateral amygdala (BLA) and prelimbic (PL) sub-region of the prefrontal cortex were evaluated on the extinction process of conditioned fear. Methods: This study was performed on 35 male Wistar rats in the weight range of 220 – 250 g. After selecting the animals, they were separated into five groups. Then, we did stereotactic surgery on rats for electrode implantation. After recovery, some rats were conditioned, followed by a 10-day treatment schedule via high-frequency DBS in the BLA or PL. Next, freezing behavior was measured as a predicted response dedicated to extinction, without shock (re-exposure). In addition, we used ELISA and Western blot to estimate blood serum corticosterone levels and c-Fos protein expression. Results: The mean freezing time recorded for the PL group was significantly lower than that of both the BLA group and the PC group (P < 0.01). The BLA group and PC group were also significantly different (P < 0.001). Corticosterone results indicated that the PL group had significantly higher serum corticosterone levels compared with both the BLA group and the PC group (P < 0.01). In addition, the BLA group revealed a significant reduction in c-Fos expression compared with the PC (P < 0.001). Conclusions: This study provides further evidence for the contribution of the prelimbic cortex and amygdala both in acquisition and extinction processes during contextual fear conditioning. However, the PL stimulation by high-frequency DBS might be more involved in the extinction process and play a more important role as an enhancer.