Stress-Enhanced Fear Learning, a Robust Rodent Model of Post-Traumatic Stress Disorder

Rajbhandari, Abha K.; Gonzalez, Sarah T.; Fanselow, Michael S.

doi:10.3791/58306

Cited by 33 publications

(31 citation statements)

References 15 publications

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“…(1) Many models with face validity use psychogenic stress with hippocampal involvement in the stress response (Jankord and Herman, 2008;Matar et al, 2013) but without physical trauma. Examples include: inescapable electrical shock (Nalloor et al, 2011;Bali and Jaggi, 2015), predator-stress (Zoladz et al, 2015), single prolonged stress (Liberzon et al, 1997), social defeat stress (Hammels et al, 2015), or a combination of these as in the SEFL (Stress Enhanced Fear Learning) model (Rajbhandari et al, 2018) and unpredictable variable stress model (van Riel et al, 2003). Rodents subjected to psychogenic trauma exhibit one or more PTSD-like symptoms identified in the DSM 5 symptom clusters described in Tables 1, 2) The behavioral correlates to PTSD symptom clusters can be reliably evaluated in animals via well-established tests of anxiety-like behavior, hyperarousal, cognitive function, and memory (see Table 1).…”

Section: Modeling a Ptsd-like Phenotype In Animalsmentioning

confidence: 99%

“…Among the many animal models of a PTSD-like phenotype, few have explicitly attempted studying susceptibility (Cohen et al, 2003(Cohen et al, , 2006b(Cohen et al, , 2012van Riel et al, 2003;Adamec et al, 2006;Gruene et al, 2015;Toth et al, 2016;Rajbhandari et al, 2018;Deslauriers et al, 2019 Reviews Yehuda andAntelman, 1993;Deslauriers et al, 2018;Fenster et al, 2018). Additionally, most of the models that have assessed susceptibility have done so using varied peri-or post-trauma behaviors.…”

Section: Sequalae Factors: Animal Models Of Susceptibility To a Ptsd-mentioning

confidence: 99%

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Investigating Individual Pre-trauma Susceptibility to a PTSD-Like Phenotype in Animals

Alexander

Nalloor

Bunting

et al. 2020

Front. Syst. Neurosci.

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• Susceptibility to developing a PTSD-like phenotype exists in animals. It can be identified behaviorally and therefore can be studied. • Susceptibility can be studied by identifying susceptibility factors (pre-trauma) and sequalae factors (peri-and posttrauma) to a PTSD-like phenotype. • Some susceptible individuals have impaired functioning in the hippocampus BEFORE emotional trauma. • Understanding susceptibility can inform ways to successfully build resilience. • Investigations into susceptibility also highlight the important idea that susceptibility is a dynamic feature of PTSD. Susceptibility is not strictly determined by genetics but requires an interaction with environmental factors, making it modifiable over time.

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Section: Modeling a Ptsd-like Phenotype In Animalsmentioning

confidence: 99%

Section: Sequalae Factors: Animal Models Of Susceptibility To a Ptsd-mentioning

confidence: 99%

Investigating Individual Pre-trauma Susceptibility to a PTSD-Like Phenotype in Animals

Alexander

Nalloor

Bunting

et al. 2020

Front. Syst. Neurosci.

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“…The impact of chronic opioid exposure on fear learning was first assessed using the SEFL model for PTSD, which captures the sensitization of fear learning observed following traumatic experience ( Fig. 1a), in addition to several other phenotypes relevant to PTSD [13,14,16]. Because prior trauma is a major predictor of who will develop PTSD in response to a subsequent traumatic event [1,18] this phenomenon is highly relevant to understanding PTSD development.…”

Section: Chronic Opioid Pretreatment Potentiates Seflmentioning

confidence: 99%

“…Here, we assessed the impact of chronic opioid regimens on the subsequent development of PTSD-like behaviors using the stress-enhanced fear learning (SEFL) model. We have previously demonstrated that SEFL captures several lasting anxiogenic changes in response to traumatic stress, including augmented fear learning, increased anxiety and startle responses, and altered glucocorticoid cycling [10][11][12][13][14]. Moreover, this model has recently been used to characterize long-lasting trauma-induced changes in drug seeking [15], making it optimal to study bidirectional interactions between trauma and drug use.…”

Section: Introductionmentioning

confidence: 99%

Chronic opioid pretreatment potentiates the sensitization of fear learning by trauma

Pennington

Fanselow

Rajbhandari

et al. 2019

Neuropsychopharmacol.

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Despite the large comorbidity between PTSD and opioid use disorders, as well as the common treatment of physical injuries resulting from trauma with opioids, the ability of opioid treatments to subsequently modify PTSD-related behavior has not been well studied. Using the stress-enhanced fear learning (SEFL) model for PTSD, we characterized the impact of chronic opioid regimens on the sensitization of fear learning seen following traumatic stress in mice. We demonstrate for the first time that chronic opioid pretreatment is able to robustly augment associative fear learning. Highlighting aversive learning as the cognitive process mediating this behavioral outcome, these changes were observed after a considerable period of drug cessation, generalized to learning about multiple aversive stimuli, were not due to changes in stimulus sensitivity or basal anxiety, and correlated with a marker of synaptic plasticity within the basolateral amygdala. Additionally, these changes were not observed when opioids were given after the traumatic event. Moreover, we found that neither reducing the frequency of opioid administration nor bidirectional manipulation of acute withdrawal impacted the subsequent enhancement in fear learning seen. Given the fundamental role of associative fear learning in the generation and progression of PTSD, these findings are of direct translational relevance to the comorbidity between opioid dependence and PTSD, and they are also pertinent to the use of opioids for treating pain resulting from traumas involving physical injuries.

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“…One criteria used to assess stress susceptibility is anxiety, despite the revision of the criteria for PTSD in the DSM-5 [12][13][14]. The stress-enhanced fear learning (SEFL) paradigm, with exposure to brief stresses rather than chronic stress, has been used to help distinguish trauma-related disorders from anxiety disorders [14][15][16]. However, a large number of behavioral tests are required to rmly verify whether each animal is susceptible or resilient to stressors, which are at risk of involving complications from various genetic factors for different behaviors [17,18].…”

Section: Introductionmentioning

confidence: 99%

Fear response-based prediction for stress susceptibility to PTSD-like phenotypes

Jeong

Lee

Sung

et al. 2020

Preprint

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Most individuals undergo traumatic stresses at some points in their life, but only a small proportion develop stress-related disorders such as anxiety diseases and posttraumatic stress disorder (PTSD). Although stress susceptibility is one determinant of mental disorders, the underlying mechanisms and functional implication remain unclear yet. We found that an increased amount of freezing that animals exhibited in the intertrial interval (ITI) of a stress-enhanced fear learning paradigm, predicts ensuing PTSD-like symptoms whereas resilient mice show ITI freezing comparable to that of unstressed mice. To examine the behavioral features, we developed a systematic analytical approach for ITI freezing and stress susceptibility. Thus, we provide a behavioral parameter for prognosis to stress susceptibility of individuals in the development of PTSD-like symptoms as well as a new mathematical means to scrutinize freezing behavior.

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Stress-Enhanced Fear Learning, a Robust Rodent Model of Post-Traumatic Stress Disorder

Cited by 33 publications

References 15 publications

Investigating Individual Pre-trauma Susceptibility to a PTSD-Like Phenotype in Animals

Investigating Individual Pre-trauma Susceptibility to a PTSD-Like Phenotype in Animals

Chronic opioid pretreatment potentiates the sensitization of fear learning by trauma

Fear response-based prediction for stress susceptibility to PTSD-like phenotypes

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