Prolonged fear incubation leads to generalized avoidance behavior in mice

Pamplona, Fabrício A.; Henes, K.; Micale, Vincenzo; Mauch, C.; Takahashi, Reinaldo Ν.; Wotjak, Carsten T.

doi:10.1016/j.jpsychires.2010.06.015

Cited by 66 publications

(59 citation statements)

References 18 publications

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“…These findings indicate that environmental cues, such as an odor or a tone present during the trauma, can be associated with the traumatic event. The present results indicate that one of the more reliable PTSD symptom described in human, avoidance, rarely explored in animal models of PTSD, can be demonstrated after a traumatic event in rats [31,32]. The present results reproduce previous findings in humans reporting that trauma-related smells and sounds can serve as strong emotional reminders and thus may potentially serve to promote re-experiencing [33,34].…”

Section: Discussionsupporting

confidence: 89%

Only susceptible rats exposed to a model of PTSD exhibit reactivity to trauma-related cues and other symptoms: An effect abolished by a single amphetamine injection

Toledano

Gisquet-Verrier

2014

Behavioural Brain Research

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Section: Discussionsupporting

confidence: 89%

Only susceptible rats exposed to a model of PTSD exhibit reactivity to trauma-related cues and other symptoms: An effect abolished by a single amphetamine injection

Toledano

Gisquet-Verrier

2014

Behavioural Brain Research

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“…This suggests that fear sensitization could be the main factor accountable for the onset of PTSD-like symptoms. In this context it has to be noted that Pamplona et al (2011), using a shock intensity (1.5 mA) considerably higher than that used in our work (0.7 mA), have recently found that contextual fear conditioning and subsequent fear incubation led to a generalized avoidance behavior in mice submitted to a conditioned odor task. However, in our experiments, animals submitted to a high electric footshock (0.7 mA) showed an exploratory activity in the plus maze and social avoidance tasks, as well as stress-coping strategies in the Morris water maze, comparable to that of control mice.…”

Section: Discussionmentioning

confidence: 63%

“…Therefore, the increased anxiety levels, social withdrawal, and spatial learning deficit observed in our groups of mice submitted to a high electric footshock (0.7 mA) appear not to be correlated with a general avoidance state. Considering the work by Pamplona et al (2011), a role for the shock intensity in the onset of a general avoidance state could therefore be taken into account. Altogether, our results show that an extinction training administered within the memory reconsolidation window, when traces are supposed to be destabilized and updated, does not attenuate the expression of remote contextual fear memory in mice.…”

Section: Discussionmentioning

confidence: 99%

“…A recently established mouse model of PTSD (Siegmund and Wotjak 2007a,b;Pamplona et al 2011) was used that allows the emergence of increased avoidance of traumarelated stimuli and emotional over-reaction to unspecific "neutral" stimuli, which belong to the three clusters of PTSD symptoms (American Psychiatric Association 2000; Siegmund and Wotjak 2007a). Moreover, this model takes into account the pathological properties of fear incubation showing an increased hyperarousal with the passage of time after the traumatic experience (Siegmund and Wotjak 2007a), when remote traumatic memories are concerned.…”

mentioning

confidence: 99%

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Extinction after retrieval: Effects on the associative and nonassociative components of remote contextual fear memory

Costanzi¹,

Cannas²,

Saraulli³

et al. 2011

Learn. Mem.

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Long-lasting memories of adverse experiences are essential for individuals' survival but are also involved, in the form of recurrent recollections of the traumatic experience, in the aetiology of anxiety diseases (e.g., post-traumatic stress disorder [PTSD]). Extinction-based erasure of fear memories has long been pursued as a behavioral way to treat anxiety disorders; yet, such a procedure turns out to be transient, context-dependent, and ineffective unless it is applied immediately after trauma. Recent evidence indicates that, in both rats and humans, extinction training can prevent the return of fear if administered within the reconsolidation window, when memories become temporarily labile and susceptible of being updated. Here, we show that the reconsolidation-extinction procedure fails to prevent the spontaneous recovery of a remote contextual fear memory in a mouse model of PTSD, as well as the long-lasting behavioral abnormalities induced by traumatic experience on anxiety and in both social and cognitive domains (i.e., social withdrawal and spatial learning deficits). Such a failure appears to be related to the ineffectiveness of the reconsolidation -extinction procedure in targeting the pathogenic process of fear sensitization, a nonassociative component of traumatic memory that causes animals to react aberrantly to harmless stimuli. This indicates fear sensitization as a major target for treatments aimed at mitigating anxiety and the behavioral outcomes of traumatic experiences.

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“…We applied an FS-induced PTSD model using inbred C57BL/6NCrl mice, a strain that is susceptible to PTSD-like symptom development [16,18,27,28,29]. Using a standardized proteomics platform based on 15 N metabolic labeling and mass spectrometry, we accurately quantified and identified significantly altered protein expression levels in affected brain regions and enriched altered cellular pathways by in silico pathway analyses.…”

Section: Discussionmentioning

confidence: 99%

Fluoxetine Treatment Rescues Energy Metabolism Pathway Alterations in a Posttraumatic Stress Disorder Mouse Model

Kao

Henes

et al. 2016

Complex Psychiatry

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Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder. Several studies have attempted to characterize molecular alterations associated with PTSD, but most findings were limited to the investigation of specific cellular markers in the periphery or defined brain regions. In the current study, we aimed to unravel affected molecular pathways/mechanisms in the fear circuitry associated with PTSD. We interrogated a foot shock-induced PTSD mouse model by integrating proteomics and metabolomics profiling data. Alterations at the proteome level were analyzed using in vivo ¹⁵N metabolic labeling combined with mass spectrometry in the prelimbic cortex (PrL), anterior cingulate cortex (ACC), basolateral amygdala, central nucleus of the amygdala and CA1 of the hippocampus between shocked and nonshocked (control) mice, with and without fluoxetine treatment. In silico pathway analyses revealed an upregulation of the citric acid cycle pathway in PrL, and downregulation in ACC and nucleus accumbens (NAc). Chronic fluoxetine treatment prevented decreased citric acid cycle activity in NAc and ACC and ameliorated conditioned fear response in shocked mice. Our results shed light on the role of energy metabolism in PTSD pathogenesis and suggest potential therapy through mitochondrial targeting.

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Prolonged fear incubation leads to generalized avoidance behavior in mice

Cited by 66 publications

References 18 publications

Only susceptible rats exposed to a model of PTSD exhibit reactivity to trauma-related cues and other symptoms: An effect abolished by a single amphetamine injection

Only susceptible rats exposed to a model of PTSD exhibit reactivity to trauma-related cues and other symptoms: An effect abolished by a single amphetamine injection

Extinction after retrieval: Effects on the associative and nonassociative components of remote contextual fear memory

Fluoxetine Treatment Rescues Energy Metabolism Pathway Alterations in a Posttraumatic Stress Disorder Mouse Model

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