title: Traumatic stress causes distinctive effects on fear circuit catecholamines and the fear extinction profile in a rodent model of posttraumatic stress disorder.
abstract: Central catecholamines regulate fear memory across the medial prefrontal cortex (mPFC), amygdala (AMYG), and hippocampus (HPC). However, inadequate evidence exists to address the relationships among these fear circuit areas in terms of the fear symptoms of posttraumatic stress disorder (PTSD). By examining the behavioral profile in a Pavlovian fear conditioning paradigm together with tissue/efflux levels of dopamine (DA) and norepinephrine (NE) and their reuptake abilities across the fear circuit areas in rats that experienced single prolonged stress (SPS, a rodent model of PTSD), we demonstrated that SPS-impaired extinction retrieval was concomitant with the changes of central DA/NE in a dissociable manner. For tissue levels, diminished DA and increased NE were both observed in the mPFC and AMYG. DA efflux and synaptosomal DA transporter were consistently reduced in the AMYG/vHPC, whereas SPS reduced NE efflux in the infralimbic cortex and synaptosomal NE transporter in the mPFC. Furthermore, a lower expression of synaptosomal VMAT2 was observed in the mPFC, AMYG, and vHPC after SPS. Finally, negative correlations were observed between retrieval freezing and DA in the mPFC/AMYG; nevertheless, the phenomena became invalid after SPS. Our results suggest that central catecholamines are crucially involved in the retrieval of fear extinction in which DA and NE play distinctive roles across the fear circuit areas.
authors: Department of Physiology, National Defense Medical Center, Taipei, Taiwan.
authors: Chen-Cheng
authors: CC
authors: Lin
authors: Division of Medical Research and Education, Cheng Hsin General Hospital, Taipei, Taiwan.
authors: Che-Se
authors: CS
authors: Tung
authors: Department of Physiology, National Defense Medical Center, Taipei, Taiwan.
authors: Pin-Hsuan
authors: PH
authors: Lin
authors: Medical Research Center, Cardinal Tien Hospital, New Taipei City, Taiwan.
authors: Chuen-Lin
authors: CL
authors: Huang
authors: Department of Physiology, National Defense Medical Center, Taipei, Taiwan; Department of Psychiatry, Tri-Service General Hospital, Taipei, Taiwan. Electronic address: yiaping@ndmctsgh.edu.tw.
authors: Yia-Ping
authors: YP
authors: Liu
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D003214:Conditioning, Classical / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D005108:Extinction, Psychological / Q000502:physiology*; D005110:Extracellular Space / Q000378:metabolism; D005239:Fear / Q000502:physiology*; D046352:Freezing Reaction, Cataleptic / Q000502:physiology; D006339:Heart Rate / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009434:Neural Pathways / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D011897:Random Allocation; D017208:Rats, Wistar; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism* / Q000523:psychology; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D004298:Dopamine; D003345:Corticosterone; D009638:Norepinephrine
keywords: Dopamine; Extinction retrieval; Fear circuit; Fear memory; Norepinephrine; Posttraumatic stress disorder