scholarly journals Behavioral Expression of Contextual Fear in Male and Female Rats

2021 ◽  
Vol 15 ◽  
Author(s):  
Amanda S. Russo ◽  
Ryan G. Parsons
Keyword(s):  
Fear Conditioning ◽  
Freezing Behavior ◽  
Contextual Fear Conditioning ◽  
Female Rats ◽  
Post Traumatic Stress ◽  
Male And Female ◽  
Contextual Fear ◽  
Male And Female Rats ◽  
Fear Potentiated Startle ◽  
Fear And Anxiety

The study of fear conditioning has led to a better understanding of fear and anxiety-based disorders such as post-traumatic stress disorder (PTSD). Despite the fact many of these disorders are more common in women than in men, the vast majority of work investigating fear conditioning in rodents has been conducted in males. The goal of the work presented here was to better understand how biological sex affects contextual fear conditioning and expression. To this end, rats of both sexes were trained to fear a specific context and fear responses were measured upon re-exposure to the conditioning context. In the first experiment, male and female rats were given context fear conditioning and tested the next day during which freezing behavior was measured. In the second experiment, rats were trained and tested in a similar fashion while fear-potentiated startle and defecation were measured. We found that males showed more freezing behavior than females during a fear expression test. The expression of fear-potentiated startle did not differ between sexes, while males exhibited more defecation during a test in a novel context. These data suggest that the expression of defensive behavior differs between sexes and highlight the importance of using multiple measures of fear when comparing between sexes.

scholarly journals Stress before Puberty Exerts a Sex- and Age-Related Impact on Auditory and Contextual Fear Conditioning in the Rat

2007 ◽  
Vol 2007 ◽  
pp. 1-12 ◽  
Author(s):  
Maria Toledo-Rodriguez ◽  
Carmen Sandi
Keyword(s):  
Fear Conditioning ◽  
Conditioned Fear ◽  
Early Adulthood ◽  
Contextual Fear Conditioning ◽  
Female Rats ◽  
Adult Males ◽  
Contextual Fear ◽  
Male And Female Rats ◽  
Age Related ◽  
The Impact

Adolescence is a period of major physical, hormonal, and psychological changes. It is also characterized by a significant increase in the incidence of psychopathologies and this increase is gender-specific. Stress during adolescence is associated with the development of psychiatric disorders later in life. In this study, we evaluated the impact of psychogenic stress (exposure to predator odor followed by placement on an elevated platform) experienced before puberty (days 28–30) on fear memories and hormonal response of male and female rats during adolescence and early adulthood. Stress before puberty impacted in a sex- and age-specific way on the responses to auditory and contextual fear conditioning in adolescence and adulthood: (a) increased conditioned fear to the tone in males during adolescence but not during adulthood; (b) impaired extinction to the tone in adult males; and (c) reduced freezing responses to the context in adolescent females. Stress before puberty did not influence the corticosterone levels 30 minutes after an additional stressor given in adulthood. These results indicate that stress experienced prior to puberty can exert a sex-related differential impact on fear-related behaviors displayed by individuals during late adolescence and early adulthood.

Translational Research from Animals to Humans

2016 ◽  
Author(s):  
Shigeru Morinobu ◽  
Shigeto Yamamoto ◽  
Manabu Fuchikami
Keyword(s):  
Animal Model ◽  
Fear Conditioning ◽  
Fear Extinction ◽  
Contextual Fear Conditioning ◽  
Behavioral Characteristics ◽  
Post Traumatic Stress ◽  
Contextual Fear ◽  
Glycine Transporter 1 ◽  
Post Traumatic ◽  
Prolonged Stress

To elucidate the pathophysiology of post-traumatic stress disorder (PTSD), the establishment of an appropriate animal model is necessary. In a series of studies, the authors validated single prolonged stress (SPS) as a model for PTSD. SPS-treated rats mimic the pathophysiological abnormalities and behavioral characteristics of PTSD, such as enhanced anxiety-like behavior, glucocorticoid negative feedback, and analgesia. In addition, the authors demonstrated enhanced freezing in response to contextual fear conditioning, and impaired extinction of fear memory, which was alleviated by D-cycloserine (DCS). In parallel, there was a decrease in extracellular glycine mediated by an increase in glycine transporter 1 in the hippocampus of SPS-treated rats after fear conditioning, which suggested that activation of N-methyl-D-asparate receptor by DCS during fear extinction training might alleviate the impaired fear extinction. This chapter summarizes PTSD-like symptoms in SPS and evaluates the validity of SPS as an animal model of PTSD.

scholarly journals Proteomic Analysis Reveals Sex-Specific Protein Degradation Targets in the Amygdala During Fear Memory Formation

2021 ◽  
Vol 14 ◽  
Author(s):  
Kayla Farrell ◽  
Madeline Musaus ◽  
Shaghayegh Navabpour ◽  
Kiley Martin ◽  
W. Keith Ray ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Fear Conditioning ◽  
Degradation Process ◽  
Fear Memory ◽  
Memory Formation ◽  
Contextual Fear Conditioning ◽  
Female Rats ◽  
Protein Targets ◽  
Male And Female Rats ◽  
Ubiquitin Proteasome

Ubiquitin-proteasome mediated protein degradation has been widely implicated in fear memory formation in the amygdala. However, to date, the protein targets of the proteasome remain largely unknown, limiting our understanding of the functional significance for protein degradation in fear memory formation. Additionally, whether similar proteins are targeted by the proteasome between sexes has yet to be explored. Here, we combined a degradation-specific K48 Tandem Ubiquitin Binding Entity (TUBE) with liquid chromatography mass spectrometry (LC/MS) to identify the target substrates of the protein degradation process in the amygdala of male and female rats following contextual fear conditioning. We found that males (43) and females (77) differed in the total number of proteins that had significant changes in K48 polyubiquitin targeting in the amygdala following fear conditioning. Many of the identified proteins (106) had significantly reduced levels in the K48-purified samples 1 h after fear conditioning, suggesting active degradation of the substrate due to learning. Interestingly, only 3 proteins overlapped between sexes, suggesting that targets of the protein degradation process may be sex-specific. In females, many proteins with altered abundance in the K48-purified samples were involved in vesicle transport or are associated with microtubules. Conversely, in males, proteins involved in the cytoskeleton, ATP synthesis and cell signaling were found to have significantly altered abundance. Only 1 protein had an opposite directional change in abundance between sexes, LENG1, which was significantly enhanced in males while lower in females. This suggests a more rapid degradation of this protein in females during fear memory formation. Interestingly, GFAP, a critical component of astrocyte structure, was a target of K48 polyubiquitination in both males and females, indicating that protein degradation is likely occurring in astrocytes following fear conditioning. Western blot assays revealed reduced levels of these target substrates following fear conditioning in both sexes, confirming that the K48 polyubiquitin was targeting these proteins for degradation. Collectively, this study provides strong evidence that sex differences exist in the protein targets of the degradation process in the amygdala following fear conditioning and critical information regarding how ubiquitin-proteasome mediated protein degradation may contribute to fear memory formation in the brain.

scholarly journals Behavioral and brain mechanisms mediating conditioned flight behavior in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michael S. Totty ◽  
Naomi Warren ◽  
Isabella Huddleston ◽  
Karthik R. Ramanathan ◽  
Reed L. Ressler ◽  
...  
Keyword(s):  
Compound Stimulus ◽  
Brain Regions ◽  
Female Rats ◽  
Flight Behavior ◽  
Central Nucleus ◽  
Male And Female ◽  
Bed Nucleus ◽  
Contextual Fear ◽  
Male And Female Rats ◽  
Context Dependent

AbstractEnvironmental contexts can inform animals of potential threats, though it is currently unknown how context biases the selection of defensive behavior. Here we investigated context-dependent flight responses with a Pavlovian serial-compound stimulus (SCS) paradigm that evokes freeze-to-flight transitions. Similar to previous work in mice, we show that male and female rats display context-dependent flight-like behavior in the SCS paradigm. Flight behavior was dependent on contextual fear insofar as it was only evoked in a shock-associated context and was reduced in the conditioning context after context extinction. Flight behavior was only expressed to white noise regardless of temporal order within the compound. Nonetheless, rats that received unpaired SCS trials did not show flight-like behavior to the SCS, indicating it is associative. Finally, we show that pharmacological inactivation of two brain regions critical to the expression of contextual fear, the central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST), attenuates both contextual fear and flight responses. All of these effects were similar in male and female rats. This work demonstrates that contextual fear can summate with cued and innate fear to drive a high fear state and transition from post-encounter to circa-strike defensive modes.

Contextual fear cues inhibit eating in food-deprived male and female rats

Appetite ◽  
2013 ◽  
Vol 69 ◽  
pp. 186-195 ◽  
Author(s):  
Christina J. Reppucci ◽  
Meghana Kuthyar ◽  
Gorica D. Petrovich
Keyword(s):  
Female Rats ◽  
Male And Female ◽  
Contextual Fear ◽  
Male And Female Rats

scholarly journals Distinct Contributions of Median Raphe Nucleus to Contextual Fear Conditioning and Fear-Potentiated Startle

2002 ◽  
Vol 9 (4) ◽  
pp. 233-247 ◽  
Author(s):  
R. C. B. Silva ◽  
A. P. M. Cruz ◽  
V. Avanzi ◽  
J. Landeira-Fernandez ◽  
M. L. Brandão
Keyword(s):  
Fear Conditioning ◽  
Conditioned Fear ◽  
Raphe Nucleus ◽  
Contextual Fear Conditioning ◽  
Median Raphe ◽  
Median Raphe Nucleus ◽  
Contextual Fear ◽  
Electrolytic Lesions ◽  
Fear Potentiated Startle ◽  
Median Raphé

Ascending 5-HT projections from the median raphe nucleus (MRN), probably to the hippocampus, are implicated in the acquisition of contextual fear (background stimuli), as assessed by freezing behavior. Foreground cues like light, used as a conditioned stimulus (CS) in classical fear conditioning, also cause freezing through thalamic transmission to the amygdala. As the MRN projects to the hippocampus and amygdala, the role of this raphe nucleus in fear conditioning to explicit cues remains to be explained. Here we analyzed the behavior of rats with MRN electrolytic lesions in a contextual conditioning situation and in a fear-potentiated startle procedure. The animals received MRN electrolytic lesions either before or on the day after two consecutive training sessions in which they were submitted to 10 conditioning trials, each in an experimental chamber (same context) where they. received foot-shocks (0.6 mA, 1 sec) paired to a 4-sec light CS. Seven to ten days later, the animals were submitted to testing sessions for assessing conditioned fear when they were placed for five shocks, and the duration of contextual freezing was recorded. The animals were then submitted to a fear-potentiated startle in response to a 4-sec light-CS, followed by white noise (100 dB, 50 ms). Control rats (sham) tested in the same context showed more freezing than did rats with pre- or post-training MRN lesions. Startle was clearly potentiated in the presence of light CS in the sham-lesioned animals. Whereas pretraining lesions reduced both freezing and fear-potentiated startle, the post-training lesions reduced only freezing to context, without changing the fear-potentiated startle. In a second experiment, neurotoxic lesions of the MRN with local injections of N-methyl-D-aspartate or the activation of5-HT1Asomatodendritic auto-receptors of the MRN by microinjections of the5-HT1Areceptor agonist 8-hydroxy- 2-(di-n-propylamino)tetralin (8-OH-DPAT) before the training sessions also reduced the amount of freezing and the fear-potentiated startle. Freezing is a prominent response of contextual fear conditioning, but does not seem to be crucial for the enhancement of the startle reflex by explicit aversive cues. As fear-potentiated startle may be produced in posttraining lesioned rats that are unable to freeze to fear contextual stimuli, dissociable systems seem to be recruited in each condition. Thus, contextual fear and fear-potentiated startle are conveyed by distinct 5-HT-mediated circuits of the MRN.

scholarly journals Relationship between footshock intensity, post-training corticosterone release and contextual fear memory specificity over time

2019 ◽  
Author(s):  
Moisés dos Santos Corrêa ◽  
Barbara dos Santos Vaz ◽  
Gabriel David Vieira Grisanti ◽  
Joselisa Péres Queiroz de Paiva ◽  
Paula Ayako Tiba ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Plasma Corticosterone ◽  
Contextual Fear Conditioning ◽  
The Novel ◽  
Post Traumatic Stress ◽  
Contextual Fear ◽  
Memory Specificity ◽  
Post Traumatic ◽  
Corticosterone Release ◽  
Training Protocols

ABSTRACTOvergeneralized fear has long been implicated in generalized anxiety and post-traumatic stress disorder, however, time-dependent mechanisms underlying memory retrieval are still not completely understood. Previous studies have revealed that stronger fear conditioning training protocols are associated with both increased post-training corticosterone (CORT) levels and fear responses at later retrieval tests. Here we used discriminative contextual fear conditioning (CFC) to investigate the relationship between post-training CORT levels and memory specificity in different retrieval timepoints. Wistar rats were exposed to CFC training with increasing footshock intensities (0.3, 0.6 or 1.0mA) and had their blood collected 30 min afterwards to measure post-training plasma CORT. After 2, 14 or 28 days, rats were tested for memory specificity either in the training or in the novel context. Regression analysis was used to verify linear and non-linear interactions between CORT levels and freezing. Higher footshock intensities increased post-training CORT levels and freezing times during tests in all timepoints. Moreover, stronger trainings elicited faster memory generalization, which was associated with higher CORT levels during memory consolidation. The 0.3mA training maintained memory specificity up to 28 days. Additionally, linear regressions suggest that the shift from specific to generalized memories is underway at 14 days after training. These results are consistent with the hypotheses that stronger training protocols elicit a faster generalization rate, and that this process is associated with increased post-training CORT release.HIGHLIGHTSStronger contextual fear conditioning (CFC) elicits higher plasma corticosterone (CORT).Strong CFC and high CORT levels increase the rate of memory generalization.Weak CFC and low CORT levels retain memory specificity up to 28 days.Post-training plasma CORT is linearly associated with remote generalized fear.

Early life stress impairs fear conditioning in adult male and female rats

2006 ◽  
Vol 1087 (1) ◽  
pp. 142-150 ◽  
Author(s):  
Therese A. Kosten ◽  
Hongjoo J. Lee ◽  
Jeansok J. Kim
Keyword(s):  
Fear Conditioning ◽  
Adult Male ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats
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