Basolateral amygdala but not medial prefrontal cortex contributes to chronic fluoxetine treatments for PTSD symptoms in mice

Abstract

Do chronic fluoxetine treatments reduced footshock-induced posttraumatic stress disorder (PTSD) symptoms, including fear and comorbid depression, in the situational reminder phase? Moreover, are the subareas of the medial prefrontal cortex (mPFC), including the cingulate cortex 1 (Cg1), prelimbic cortex (PrL), infralimbic cortex (IL), and basolateral amygdala (BLA), involved in the fluoxetine amelioration of PTSD symptoms? These two crucial issues were addressed in the present study. All mice were injected with chronic fluoxetine or normal saline treatments for the adaptation (14 days), footshock fear conditioning (1 day), and situational reminder (3 days) phases. After adaptation, the mice were subjected to footshock (2 mA, 10 seconds) or nonfootshock and stayed 2 min in a footshock box for 2 min for fear conditioning. Later, they were placed in the footshock box for 2 min in the situational reminder phase. In the final session of the situational reminder phase, a forced swimming test (FST) and immunohistochemical staining were conducted. The results indicated that footshock induced fear and comorbid depression. Meanwhile, chronic fluoxetine treatments reduced fear and depression behaviors. The Cg1, PrL, IL, and BLA were seemingly to increase c-Fos expression after footshock-induced PTSD symptoms in the situational reminder phase. The fluoxetine treatments reduced only the BLA’s c-Fos expression. The findings suggest that BLA contributes to the fluoxetine amelioration of PTSD symptoms; however, the mPFC, including the Cg1, PrL, and IL, did not mediate PTSD symptoms’ amelioration stemming from fluoxetine. The present data might help us to further understand the neural mechanism of fluoxetine treatments in PTSD symptoms.