Contribution of Hippocampal 5-HT3 Receptors in Hippocampal Autophagy and Extinction of Conditioned Fear Responses after a Single Prolonged Stress Exposure in Rats

Wu, Zhi‐Ying; Yang, Lihua; Cui, Rong; Ni, Gui-Lian; Wu, Fengtian; Liang, Yong

doi:10.1007/s10571-016-0395-7

Cited by 15 publications

(6 citation statements)

References 82 publications

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“…2). This finding is in line with the results of a few other studies that have examined extinction in SPS animals (Knox et al ., 2012; Wu et al ., 2017).…”

Section: Discussionmentioning

confidence: 99%

“…Each rat was put in the center of the maze, and the total time spent in open/closed arms or the total entry to the open/closed arms was measured for 5 min. The percentage of time spent in the open arms and entries to the open arms were calculated in relation to the total time spent or entry to the open plus close arms, respectively (Wu et al ., 2017).…”

Section: Methodsmentioning

confidence: 99%

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Sodium butyrate enhances fear extinction and rescues hippocampal acetylcholinesterase activity in a rat model of posttraumatic stress disorder

Mohammadi-Farani¹,

Limoee

Shirooie³

2021

Behavioural Pharmacology

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It is believed that impaired extinction of fear memories is an underlying cause for the development of posttraumatic stress disorder (PTSD). Histone deacetylases (HDAC) are enzymes that modulate extinction by changing the chromatin structure and altering protein synthesis in the brain. Studies show that stress modifies both HDAC activity and cerebral cholinergic neurotransmission. The present work aims to evaluate the effect of sodium butyrate (NaBu), an HDAC inhibitor, on behavioral markers of extinction and biochemical changes in HDAC and acetylcholinesterase activity in the hippocampus. NaBu was administered for 7 days in a group of rats that were exposed to single prolonged stress (SPS), as a model for PTSD. Contextual fear conditioning was performed on the 8th day, and fear extinction was measured in the next 4 consecutive days. Other behavioral tests to measure anxiety, locomotor activity and working memory were performed for further interpretation of the results. Hippocampal acetylcholinesterase and HDAC activity were also measured through biochemical tests. Behavioral results showed that treatment with NaBu can reverse the SPS-induced extinction deficits. Biochemical data indicated that while SPS induced overactivity in hippocampal HDAC, it decreased acetylcholinesterase activity in the region. Both effects were reversed after NaBu treatment. It seems that at least part of extinction deficiency in SPS exposed rats is related to hypoacetylation of acetylcholinesterase in the hippocampus. Preemptive therapy with an HDAC inhibitor reverses this process and is worth further evaluation as a possible therapeutic approach in PTSD.

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“…2). This finding is in line with the results of a few other studies that have examined extinction in SPS animals (Knox et al ., 2012; Wu et al ., 2017).…”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Sodium butyrate enhances fear extinction and rescues hippocampal acetylcholinesterase activity in a rat model of posttraumatic stress disorder

Mohammadi-Farani¹,

Limoee

Shirooie³

2021

Behavioural Pharmacology

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“…In contrast, SPS decreases HC expression of 5-HT3A receptors, which are thought to be involved in neurogenesis and antidepressant effects ( 272 ). This change has been indirectly linked to PTSD symptomology by the finding that an intrahippocampal 5-HT3A receptor agonist infused immediately after SPS blocked fear extinction deficits ( 181 ). SPS might also affect 5-HT release and/or reuptake, as 5-HT concentrations are increased in the HC following SPS ( 183 ) and 5-HT reuptake transporter (SERT) knockdown in dorsal raphe projection neurons prevented SPS-induced fear extinction deficits ( 182 ).…”

Section: Neural and Molecular Mechanisms In Spsmentioning

confidence: 99%

Single-Prolonged Stress: A Review of Two Decades of Progress in a Rodent Model of Post-traumatic Stress Disorder

et al. 2018

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Post-traumatic stress disorder (PTSD) is a common, costly, and often debilitating psychiatric condition. However, the biological mechanisms underlying this disease are still largely unknown or poorly understood. Considerable evidence indicates that PTSD results from dysfunction in highly-conserved brain systems involved in stress, anxiety, fear, and reward. Pre-clinical models of traumatic stress exposure are critical in defining the neurobiological mechanisms of PTSD, which will ultimately aid in the development of new treatments for PTSD. Single prolonged stress (SPS) is a pre-clinical model that displays behavioral, molecular, and physiological alterations that recapitulate many of the same alterations observed in PTSD, illustrating its validity and giving it utility as a model for investigating post-traumatic adaptations and pre-trauma risk and protective factors. In this manuscript, we review the present state of research using the SPS model, with the goals of (1) describing the utility of the SPS model as a tool for investigating post-trauma adaptations, (2) relating findings using the SPS model to findings in patients with PTSD, and (3) indicating research gaps and strategies to address them in order to improve our understanding of the pathophysiology of PTSD.

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“…Conditioning and extinction procedures were adopted from the previous report( 20 ) with slight modifications. First, rats were acclimatized to the conditioning chamber for 1 min, next they went through the training phase by receiving four trials of conditioning.…”

Section: Methodsmentioning

confidence: 99%

Sex differences in acetylcholinesterase modulation during spatial and fear memory extinction in the amygdala; an animal study in the single prolonged stress model of PTSD

2022

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Background and purpose: Men and women show different reactions to trauma and that is believed to be the reason behind the higher prevalence of post-traumatic stress disorder (PTSD) in women. Cholinergic signaling has long been known to be involved in the processing of fear-related information and the amygdala is a critical center for fear modulation. The main goal of the current research was to find (a) whether trauma results in different learning/extinction of fear or spatial-related information among male and female rats and (b) if trauma is associated with different acetylcholinesterase (AchE) activity in the amygdala. Experimental approach: We used single prolonged stress (SPS) as a PTSD model in this study. Normal and SPS animals of both sexes were tested in contextual and spatial tasks (learning and extinction). AchE activity in the amygdala was also measured during each process. Findings / Results: Results indicated that fear and spatial learning were impaired in SPS animals. SPS animals also had deficits in fear and spatial memory extinction and the effect was significantly higher in female- SPS than in the male-SPS group. In the enzymatic tests, AchE activity was increased during the fear extinction test and incremental changes were more significant in the female-SPS group. Conclusion and implications: Collectively, these findings provided evidence that sex differences in response to trauma were at least partly related to less fear extinction potential in female subjects. It also indicated that the extinction deficit was associated with reduced cholinergic activity in the amygdala of female animals.

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Contribution of Hippocampal 5-HT3 Receptors in Hippocampal Autophagy and Extinction of Conditioned Fear Responses after a Single Prolonged Stress Exposure in Rats

Cited by 15 publications

References 82 publications

Sodium butyrate enhances fear extinction and rescues hippocampal acetylcholinesterase activity in a rat model of posttraumatic stress disorder

Sodium butyrate enhances fear extinction and rescues hippocampal acetylcholinesterase activity in a rat model of posttraumatic stress disorder

Single-Prolonged Stress: A Review of Two Decades of Progress in a Rodent Model of Post-traumatic Stress Disorder

Sex differences in acetylcholinesterase modulation during spatial and fear memory extinction in the amygdala; an animal study in the single prolonged stress model of PTSD

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