scholarly journals Glycyrrhizin Treatment Facilitates Extinction of Conditioned Fear Responses After a Single Prolonged Stress Exposure in Rats

2018 ◽  
Vol 45 (6) ◽  
pp. 2529-2539 ◽  
Author(s):  
Shuhua Lai ◽  
Gangwei Wu ◽  
Zhixian Jiang
Keyword(s):  
Critical Role ◽  
Fear Memory ◽  
Fear Extinction ◽  
Chromosomal Protein ◽  
Single Prolonged Stress ◽  
Contextual Fear ◽  
Contextual Fear Memory ◽  
Memory Extinction ◽  
Prolonged Stress ◽  
Tlr4 Antagonist

Background/Aims: Impaired fear memory extinction is widely considered a key mechanism of post-traumatic stress disorder (PTSD). Recent studies have suggested that neuroinflammation after a single prolonged stress (SPS) exposure may play a critical role in the impaired fear memory extinction. Studies have shown that high mobility group box chromosomal protein 1 (HMGB-1) is critically involved in neuroinflammation. However, the role of HMGB-1 underlying the development of impairment of fear memory extinction is still not known. Methods: Thus, we examined the levels of HMGB-1 in the basolateral amygdala (BLA) following SPS using Western blot and evaluated the levels of microglia and astrocytes activation in the BLA after SPS using immunohistochemical staining. We then examined the effects of pre-SPS intra-BLA administration of glycyrrhizin, an HMGB1 inhibitor, or LPS-RS, a competitive TLR4 antagonist, on subsequent post-SPS fear extinction. Results: We found that SPS treatment prolonged the extinction of contextual fear memory after the SPS. The impairment of SPS-induced extinction of contextual fear memory was associated with increased HMGB1 and Toll-like receptor 4 (TLR4) levels in the BLA. Additionally, the impairment of SPS-induced extinction of contextual fear memory was associated with increased activation of microglia and astrocyte in the BLA. Intra-BLA administrations of glycyrrhizin (HMGB-1 inhibitor) or LPS-RS (TLR4 antagonist) can prevent the development of SPS-induced fear extinction impairment. Conclusion: Taken together, these results suggested that SPS treatment may not only produce short term effects on the HMGB1/TLR4-mediated pro-inflammation, but alter the response of microglia and astrocytes to the exposure to fear associated contextual stimuli.

scholarly journals Role of Amygdala-Infralimbic Cortex Circuitry in Glucocorticoid-Induced Facilitation of Auditory Fear Memory Extinction

2021 ◽  
pp. 1-22
Author(s):  
Masoomeh Dadkhah ◽  
◽  
Abbas Ali Vafaei ◽  
Ali Rashidy-Pour ◽  
Parnia Trahomi ◽  
...  
Keyword(s):  
Critical Role ◽  
Fear Memory ◽  
Fear Extinction ◽  
Freezing Behavior ◽  
Extinction Training ◽  
Male Rats ◽  
Memory Extinction ◽  
The Right ◽  
Fear Expression

Purpose: The basolateral amygdala (BLA) and infralimbic area (IL) of medial prefrontal cortex (mPFC) are two inter-connected brain structures that mediate both fear memory expression and extinction. Besides the well-known role of the BLA in the acquisition and expression of fear memory, projections from IL to BLA inhibit fear expression and have a critical role in fear extinction. However, the details of IL-BLA interaction remain unclear. Here, we aimed to investigate the role of functional reciprocal interactions between BLA and IL in mediating fear memory extinction. Methods: Using lidocaine (LID), male rats underwent unilateral or bilateral inactivation of the BLA and then unilateral intra-IL infusion of CORT, prior to extinction training of auditory fear conditioning paradigm. Freezing behavior was reported as an index for the measurement of conditioned fear. Infusions were performed before the extinction training, allowing to examine the effects on fear expression and also further extinction memory. Experiments 1-3 investigated the effects of left or right infusion of CORT into IL, and LID unilaterally into BLA on fear memory extinction. Results: Results showed that intra-IL infusion of CORT in the right hemisphere reduced freezing behavior when administrated before the extinction training. Auditory fear memory extinction was impaired by asymmetric inactivation of BLA and CORT infusion in the right IL; however, the same effect was not observed with symmetric inactivation of BLA. Conclusion: It is concluded that that the IL-BLA neural circuit may provide additional evidence to contribution of this circuit in auditory fear extinction. This study demonstrate dissociable roles for right or left BLA in subserving the auditory fear extinction. Our finding also raise the possibility that left BLA-IL circuitry may contribute in mediating auditory fear memory extinction via underlying mechanisms, however further research is required.

scholarly journals Effects of Single Prolonged Stress and D-Cycloserine on Contextual Fear Extinction and Hippocampal NMDA Receptor Expression in a Rat Model of PTSD

2007 ◽  
Vol 33 (9) ◽  
pp. 2108-2116 ◽  
Author(s):  
Shigeto Yamamoto ◽  
Shigeru Morinobu ◽  
Manabu Fuchikami ◽  
Akiko Kurata ◽  
Toshiro Kozuru ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Rat Model ◽  
Fear Extinction ◽  
Receptor Expression ◽  
Single Prolonged Stress ◽  
Contextual Fear ◽  
Prolonged Stress

scholarly journals Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-βPrecursor Protein/Presenilin 2 Mouse Model of Alzheimer’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Yasushi Kishimoto ◽  
Kai Fukumoto ◽  
Mika Nagai ◽  
Ayaka Mizuguchi ◽  
Yuiko Kobashi
Keyword(s):  
Mouse Model ◽  
Critical Role ◽  
Memory Deficits ◽  
Fear Memory ◽  
Contextual Fear ◽  
Contextual Fear Memory ◽  
Model Of Alzheimer’S Disease ◽  
Swedish Mutation ◽  
Presenilin 2 ◽  
Tg2576 Mice

Presenilin 1 and presenilin 2 (PS1 and PS2) play a critical role inγ-secretase-mediated cleavage of amyloid-βprecursor protein (APP) and the subsequent generation ofβ-amyloid peptides. The purpose of the present study was to test whether PS2 mutation accelerates the onset of contextual fear memory deficits in a mouse model of AD that expresses a mutation (K670N/M671L) of the human APP with the Swedish mutation (Tg2576 mice). In the present study, an APP/PS2 double-transgenic mouse model (PS2Tg2576) was generated by crossbreeding transgenic mice carrying the human mutant PS2 (N141I) with Tg2576 mice. Contextual fear conditioning was tested in PS2Tg2576 mice aged 3, 4, 6, and 10–12 months. PS2Tg2576 mice showed a tendency of lower freezing behavior as early as 3 months of age, but significant memory impairment was observed from the age of 4 months. The cognitive impairment was more prominent at ages of 6 and 10–12 months. In contrast, Tg2576 mice aged 3 and 4 months exhibited successful acquisition of contextual fear learning, but Tg2576 mice aged 6 months or older showed significantly impaired fear memory. These results show that PS2 mutation significantly accelerates the onset of fear memory deficits in the APP AD model mice.

scholarly journals The anterior cingulate cortex and its role in controlling contextual fear memory to predatory threats

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Miguel Antonio Xavier de Lima ◽  
Marcus Vinicius C Baldo ◽  
Fernando A Oliveira ◽  
Newton Sabino Canteras
Keyword(s):  
Basolateral Amygdala ◽  
Critical Role ◽  
Fear Memory ◽  
Anterior Cingulate ◽  
Contextual Fear ◽  
Contextual Fear Memory ◽  
Life Threatening ◽  
Learned Fear ◽  
Predator Threat ◽  
Made In

Predator exposure is a life-threatening experience and elicits learned fear responses to the context in which the predator was encountered. The anterior cingulate area (ACA) occupies a pivotal position in a cortical network responsive to predatory threats, and it exerts a critical role in processing fear memory. The experiments were made in mice and revealed that the ACA is involved in both the acquisition and expression of contextual fear to predatory threat. Overall, the ACA can provide predictive relationships between the context and the predator threat and influences fear memory acquisition through projections to the basolateral amygdala and perirhinal region and the expression of contextual fear through projections to the dorsolateral periaqueductal gray. Our results expand previous studies based on classical fear conditioning and open interesting perspectives for understanding how the ACA is involved in processing contextual fear memory to ethologic threatening conditions that entrain specific medial hypothalamic fear circuits.

scholarly journals The anterior cingulate cortex and its role in controlling contextual fear memory to predatory threats

2021 ◽  
Author(s):  
Miguel Antonio Xavier de Lima ◽  
Marcus Vinicius C. Baldo ◽  
Fernando A. Oliveira ◽  
Newton Sabino Canteras
Keyword(s):  
Basolateral Amygdala ◽  
Critical Role ◽  
Fear Memory ◽  
Anterior Cingulate ◽  
Contextual Fear ◽  
Contextual Fear Memory ◽  
Life Threatening ◽  
Memory Acquisition ◽  
Learned Fear ◽  
Predator Threat

ABSTRACTPredator exposure is a life-threatening experience and elicits learned fear responses to the context in which the predator was encountered. The anterior cingulate area (ACA) occupies a pivotal position in a cortical network responsive to predatory threats, and it exerts a critical role in processing fear memory. Ours results revealed that the ACA is involved in both the acquisition and expression of contextual fear to predatory threat. Overall, the ACA can provide predictive relationships between the context and the predator threat and influences fear memory acquisition through projections to the basolateral amygdala and perirhinal region and the expression of contextual fear through projections to the dorsolateral periaqueductal gray. Our results expand previous studies based on classical fear conditioning and open interesting perspectives for understanding how the ACA is involved in processing contextual fear memory to ethologic threatening conditions that entrain specific medial hypothalamic fear circuits (i.e., predator- and conspecific-responsive circuits).

scholarly journals The role of the cannabinoid system in fear memory and extinction in male and female mice

2021 ◽  
Author(s):  
Ikumi Mizuno ◽  
Shingo Matsuda ◽  
Suguru Tohyama ◽  
Akihiro Mizutani
Keyword(s):  
Sex Differences ◽  
Molecular Mechanisms ◽  
Acid Amide ◽  
Fear Memory ◽  
Fear Extinction ◽  
Male And Female ◽  
Contextual Fear ◽  
Contextual Fear Memory ◽  
Female Mice

The prevalence of post-traumatic stress disorder (PTSD) is higher in women than in men. Among both humans and mice, females exhibit higher resistance to fear extinction than males, suggesting that differences between sexes in processes of fear extinction are involved in the pathophysiology of such fear-related diseases. Sex differences in molecular mechanisms for fear memory and extinction are unclear. The cannabinoid (CB) system is well known to be involved in fear memory and extinction, but this involvement is based mainly on experiments using male rodents. It has been unclear whether there are sex differences in the role of the CB system in fear memory and extinction. To explore the possibility of such differences, we investigated the effects of pharmacological manipulations of the CB system on the retrieval and extinction of contextual fear memory in male and female mice. WIN55,212-2, a CB receptor (CBR) agonist, augmented the retrieval of fear memory in both sexes, but SR141716 (a CB1R antagonist) did not affect it in either sex. An enhancement of 2-arachidonylglycerol (2-AG, one of the two major endocannabinoids) via JZL184 [an inhibitor of the 2-AG hydrolase monoacylglycerol lipase (MAGL)], augmented the retrieval of fear memory through the activation of CB1R but not CB2R in female mice. In contrast, the enhancement of N-arachidonylethanolamine (AEA, the other major endocannabinoid) via URB597, an inhibitor of an AEA hydrolase (fatty acid amide hydrolase-1) did not show any effects on the retrieval or extinction of fear memory in either sex. WIN55,212-2, SR141716, and JZL184 inhibited fear extinction irrespective of sex. These results suggest that although the role of CB1R in the retrieval and extinction of contextual fear memory is common among males and females, the effects of an increase in the 2-AG level on the retrieval of contextual fear memory differ between the sexes.

scholarly journals Bidirectional Effects of Cannabidiol on Contextual Fear Memory Extinction

2016 ◽  
Vol 7 ◽  
Author(s):  
Chenchen Song ◽  
Carl W. Stevenson ◽  
Francisco S. Guimaraes ◽  
Jonathan L. C. Lee
Keyword(s):  
Fear Memory ◽  
Contextual Fear ◽  
Contextual Fear Memory ◽  
Memory Extinction ◽  
Bidirectional Effects
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