The Different Effects Of Acute And Chronic Stress On Fear Conditioning And The Expression Of CRFR1 In Rats

Chronic stress often results in anxiety-like behaviors?fear-related conditioned freezing behavior and the hypertrophy and hyperactivity of the amygdala.Besides,the altered fear conditioning signaling pathway resulted from acute stress has been proved to be associated with amygdala.The amygdala is an important limbic area involved in Pavlovian fear conditioning and the dysregulation of CRF and its receptors in the amygdala can cause alteration in the anxiety response of animals.However,few studies investigate the role of acute and chronic stress in the process of formation and extinction of fear conditioning.Our aim was to study the effects of acute and chronic stress on fear conditioning and the changes of CRFR1 mRNA expression in some related brain regions.We demonstrated that when compared to control,rats exposed to acute stress showed lower freezing ratio in the acquisition and contextual related fear conditioning;by contrast,chronic stress would result in higher freezing ratio.Both acute and chronic stress could decrease the freezing ratio in fear extinction.In addition,chronic stress caused significant body weight loss and a reduction of spontaneous and exploratory behaviors in open field test.Then in situ hybridization results showed that an increased expression of CRFR1 mRNA in hippocampal CA3,in chronically stressed rats,however,rats from acute stress group showed a decreased expression levels after fear conditioning test;however,no significant difference among the three groups in BLA,mPFC.Besides,among the three subdivisions of hippocampus:DG,CA2 and CA3,CRFR1 positive cells had a higher expression than CA2 and CA3.Our study revealed that acute and chronic stress can generate opposite effects on the formation and contextual related fear conditioning;on the contrary,can produce similar effects but in different degrees on fear extinction.In addition,the mechanisms responsible for facilitating or inhibiting fear formation or extinction may be associated with CRFR1.These results suggest that different types,durations and orders of stress have distinct effects on fear conditioning behaviors,and provide evidence for an adaptive mechanism involving the action of CRFR1 in hippocampus,mPFC and BLA in response to acute and chronic stress exposure.