Effect of WIN55-212-2 and Consequences of Extinction Training on Conditioned Fear Memory in PTSD Male Rats

Ghasemi, Mohammadreza; Abrari, Kataneh; Goudarzi, Iran; Rashidy-Pour, Ali

doi:10.29252/nirp.bcn.8.6.493

Cited by 15 publications

(7 citation statements)

References 35 publications

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“…The effects of WIN and JZL on the retrieval and extinction of fear memory in the present study are inconsistent with those of many reports that the activation of CB1Rs by WIN, JZL, or other CBR agonists reduces the retrieval of fear memory and/or enhances fear extinction in male rodents (Atsak et al, 2012; Bisby et al, 2020; Bitencourt et al, 2008; CG Reich et al, 2008; Ghasemi et al, 2017; Korem et al, 2017; Kuhnert et al, 2013; Lin et al, 2009; Lisboa et al, 2015; Morena et al, 2017; Pamplona et al, 2006, 2008; Sachser et al, 2015; Segev and Akirav, 2011; Simone et al, 2015). This inconsistency may be caused by differences in experimental methods.…”

Section: Discussioncontrasting

confidence: 99%

“…Of those factors, the effect of the species is likely to affect the inconsistency the most. Our present findings are consistent with those of studies using mice (Llorente-Berzal et al, 2015) but inconsistent with those of studies using rats (Atsak et al, 2012; Bisby et al, 2020; Bitencourt et al, 2008; CG Reich et al, 2008; Ghasemi et al, 2017; Korem et al, 2017; Kuhnert et al, 2013; Lin et al, 2009; Lisboa et al, 2015; Pamplona et al, 2006, 2008; Sachser et al, 2015; Segev and Akirav, 2011; Simone et al, 2015). The hippocampal IPSCs in mice showed larger sensitivity to WIN compared to those in rats (Haller et al, 2007).…”

Section: Discussionsupporting

confidence: 55%

“…Our present findings are consistent with those of studies using mice (Llorente-Berzal et al, 2015) but inconsistent with those of studies using rats (Atsak et al, 2012;Bisby et al, 2020;Bitencourt et al, 2008;CG Reich et al, 2008;Ghasemi et al, 2017;Korem et al, 2017;Kuhnert et al, 2013;Lin et al, 2009;Lisboa et al, 2015;Pamplona et al, , 2008 . CC-BY-ND 4.0 International license made available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.…”

Section: Inconsistency With Previous Studies Using Win or Jzlsupporting

confidence: 52%

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

Mizuno

Matsuda

Tohyama

et al. 2021

Preprint

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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.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 55%

Section: Inconsistency With Previous Studies Using Win or Jzlsupporting

confidence: 52%

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

Mizuno

Matsuda

Tohyama

et al. 2021

Preprint

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“…It was found that the consolidation of fear memory was not affected in mice injected intraperitoneally with CB1R antagonists (Arenos et al, 2006 ), the retrieval of fear memory was enhanced (Niyuhire et al, 2007 ; Lemos et al, 2010 ; Lisboa et al, 2010 ), and the extinction of fear memory was impaired (Do Monte et al, 2013 ; Gunduz-Cinar et al, 2013 ). Intraperitoneal injection of WIN55,212-2 (WIN), a CB1R agonist, significantly enhances fear memory recovery, and low doses of WIN promote fear memory extinction (Ghasemi et al, 2017 ). By microinjecting CB1R agonists or antagonists into brain regions associated with fear memory, it was found that rats injected with the CB1R agonist WIN in the BLA exhibited an impairment of fear memory retrieval, with no effect on fear extinction.…”

Section: Neurobiological Mechanisms Of Fear Extinctionmentioning

confidence: 99%

Update on neurobiological mechanisms of fear: illuminating the direction of mechanism exploration and treatment development of trauma and fear-related disorders

Liu

Zhi

et al. 2023

Front. Behav. Neurosci.

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Fear refers to an adaptive response in the face of danger, and the formed fear memory acts as a warning when the individual faces a dangerous situation again, which is of great significance to the survival of humans and animals. Excessive fear response caused by abnormal fear memory can lead to neuropsychiatric disorders. Fear memory has been studied for a long time, which is of a certain guiding effect on the treatment of fear-related disorders. With continuous technological innovations, the study of fear has gradually shifted from the level of brain regions to deeper neural (micro) circuits between brain regions and even within single brain regions, as well as molecular mechanisms. This article briefly outlines the basic knowledge of fear memory and reviews the neurobiological mechanisms of fear extinction and relapse, which aims to provide new insights for future basic research on fear emotions and new ideas for treating trauma and fear-related disorders.

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“…Evidence of cannabis use for alleviating symptoms of depression in humans [ 77 ] is backed by animal research [ 15 , 78 , 79 ]. Rodent studies suggest beneficial effects of ECB signaling enhancers such as the FAAH inhibitor URB597 (URB; FAAH degrades AEA), the CB1/2 receptor agonist WIN55,212-2 (WIN), and cannabidiol (CBD; a cannabis sativa constituent) in rodent models for depression [ 15 , 80 , 81 , 82 ], anxiety, and PTSD [ 16 , 83 , 84 , 85 , 86 ]. Although there is support for a therapeutic effect of cannabinoids in humans [ 10 , 11 , 12 , 87 , 88 , 89 , 90 ], most clinical studies to date have significant limitations (e.g., small samples, low quality), complicating the establishment of recommendations for clinical cannabinoid use.…”

Section: The Endocannabinoid (Ecb) Systemmentioning

confidence: 99%

Do Adolescent Exposure to Cannabinoids and Early Adverse Experience Interact to Increase the Risk of Psychiatric Disorders: Evidence from Rodent Models

Portugalov

Akirav

2021

IJMS

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There have been growing concerns about the protracted effects of cannabis use in adolescents on emotion and cognition outcomes, motivated by evidence of growing cannabis use in adolescents, evidence linking cannabis use to various psychiatric disorders, and the increasingly perceived notion that cannabis is harmless. At the same time, studies suggest that cannabinoids may have therapeutic potential against the impacts of stress on the brain and behavior, and that young people sometimes use cannabinoids to alleviate feelings of depression and anxiety (i.e., “self-medication”). Exposure to early adverse life events may predispose individuals to developing psychopathology in adulthood, leading researchers to study the causality between early life factors and cognitive and emotional outcomes in rodent models and to probe the underlying mechanisms. In this review, we aim to better understand the long-term effects of cannabinoids administered in sensitive developmental periods (mainly adolescence) in rodent models of early life stress. We suggest that the effects of cannabinoids on emotional and cognitive function may vary between different sensitive developmental periods. This could potentially affect decisions regarding the use of cannabinoids in clinical settings during the early stages of development and could raise questions regarding educating the public as to potential risks associated with cannabis use.

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Effect of WIN55-212-2 and Consequences of Extinction Training on Conditioned Fear Memory in PTSD Male Rats

Cited by 15 publications

References 35 publications

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

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

Update on neurobiological mechanisms of fear: illuminating the direction of mechanism exploration and treatment development of trauma and fear-related disorders

Do Adolescent Exposure to Cannabinoids and Early Adverse Experience Interact to Increase the Risk of Psychiatric Disorders: Evidence from Rodent Models

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