Effects of corticosterone on contextual fear consolidation in intact and ovariectomized female rats

Kashefi, Adel; Rashidy-Pour, Ali

doi:10.1016/j.nlm.2014.06.013

Cited by 12 publications

(6 citation statements)

References 42 publications

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“…Intriguingly, as opposed to the robust protective effect on pain-intrusions, we found that higher E2 conferred greater risk for experiencing film-intrusions in the first days after analogue-trauma. Considering E2's positive effects on memory consolidation (Frick et al, 2018;Kashefi & Rashidy-Pour, 2014), our finding of initial film-intrusion-enhancing effect of E2 agrees with other research observing detrimental effects of sleep-related enhanced memory consolidation specifically on early intrusions (Porcheret et al, 2015). During memory consolidation, individuals consolidate not only contextual details, but also sensoryperceptual elements encountered during trauma (Payne et al, 2008).…”

Section: Discussionsupporting

confidence: 89%

Estradiol during (analogue-) trauma: risk- or protective factor for intrusive re-experiencing?

Franke¹,

Miedl²,

Danböck³

et al. 2021

Preprint

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Intrusions, a key symptom of posttraumatic stress disorder (PTSD), can occur as classically conditioned responses to trauma-related cues, both in the form of images and pain sensations. Women are more vulnerable to experiencing intrusions, and gonadal hormones may underlie this sex difference. Yet so far, particularly estradiol’s influence on intrusions is unclear, as PTSD-symptom studies suggesting a vulnerable window for intrusions during the high estradiol-progesterone phase diverge from fear-conditioning studies suggesting a protective role of estradiol. Here, we aim to address this discrepancy and examine the effects of estradiol on intrusions while also considering stress as potential moderator.Forty free-cycling women participated in an ecologically informed trauma-pain-conditioning (TPC) paradigm, using trauma-films and pain as unconditioned stimuli. Predictors were salivary estradiol and stress indexed by salivary cortisol and self-reported state-anxiety during TPC. Outcomes were film- and pain-intrusions occurring during daily-life in the week following TPC and a memory-triggering-task in response to conditioned stimuli 24h after TPC.Estradiol yielded time- and stress-dependent effects on film-intrusions during daily-life: women with higher estradiol showed initially greater probability of experiencing film-intrusions, switching to lower probability toward the end of the week. This late protective effect of estradiol on film-intrusions only held for higher state-anxious women. In contrast, estradiol showed consistent protective effects on pain-intrusions during daily-life and memory-triggering-task. Together, these data suggest that high estradiol during trauma may shield women from long-term audiovisual trauma intrusions, as well as from pain-intrusions, and thereby possibly constitute a protective factor for PTSD and potentially also for chronic pain.

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Section: Discussionsupporting

confidence: 89%

Estradiol during (analogue-) trauma: risk- or protective factor for intrusive re-experiencing?

Franke¹,

Miedl²,

Danböck³

et al. 2021

Preprint

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“…However, in the current study, we did not observe any effect of oestrous cycle on freezing levels. Studies on sex differences following fear conditioning have been inconsistent, with studies reporting no effects of oestrous cycle on freezing behavior (Cossio et al 2016), or decreased freezing levels in females (Maren et al 1994;Pryce et al 1999;Gupta et al 2001;Jasnow et al 2006;Chang et al 2009;Barha et al 2010;Kashefi and Rashidy-Pour 2014). Although our study cannot explain the discrepancies between these studies, we speculate that they may arise from experimental variations within the fear-conditioning paradigm animal species or strain.…”

Section: Sex Differencesmentioning

confidence: 59%

Effects of corticosterone on mild auditory fear conditioning and extinction; role of sex and training paradigm

et al. 2018

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Multiple lines of evidence suggest that glucocorticoid hormones enhance memory consolidation of fearful events. However, most of these studies involve male individuals. Since anxiety, fear, and fear-associated disorders present differently in male and female subjects we investigated in mice whether male and female mice perform differently in a mild, auditory fear conditioning task and tested the modulatory role of glucocorticoid hormones. Using an auditory fear conditioning paradigm with different footshock intensities (0.1, 0.2, and 0.4 mA) and frequencies (1× or 3×), we find that intraperitoneal injections with corticosterone (2 mg/kg) immediately after training, altered freezing behavior when repeated footshocks were applied, and that the direction of the effects were opposite in male and female mice. Effects were independent of footshock intensity. In male mice, corticosterone consistently increased freezing behavior in response to the tone, whereas in female mice, corticosterone reduced freezing behavior 24 h after training. These effects were not related to the phase of the oestrous cycle. In addition, corticosterone enhanced extinction learning for all tones, in both male and female mice. These results emphasize that glucocorticoid hormones influence memory consolidation and retrieval, and underscore sex-specific effects of glucocorticoid hormones in modulating conditioned fear responses.

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“…In support of this contention, extremely high levels of glucocorticoid ( i.e. , corticosterone in mice) disrupt the ability to learn and retrieve memories (62–66). Within minutes of stress, corticosterone promotes increased glutamate release in the hippocampus, while also enhancing the intrinsic excitability of CA1 pyramidal neurons (67–69).…”

Section: Discussionmentioning

confidence: 95%

G Protein-Gated K + Channel Ablation in Forebrain Pyramidal Neurons Selectively Impairs Fear Learning

Victoria

Velasco

Ostrovskaya

et al. 2016

Biological Psychiatry

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Background Cognitive dysfunction occurs in many debilitating conditions including Alzheimer’s disease, Down syndrome, schizophrenia, and mood disorders. The dorsal hippocampus is a critical locus of cognitive processes linked to spatial and contextual learning. G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels, which mediate the postsynaptic inhibitory effect of many neurotransmitters, have been implicated in hippocampal-dependent cognition. Available evidence, however, derives primarily from constitutive gain-of-function models that lack cellular specificity. Methods We used constitutive and neuron-specific gene ablation models targeting an integral subunit of neuronal GIRK channels (GIRK2) to probe the impact of GIRK channels on associative learning and memory. Results Constitutive Girk2−/− mice exhibited a striking deficit in hippocampal-dependent (contextual) and hippocampal-independent (cue) fear conditioning. Mice lacking GIRK2 in GABA neurons (GAD-Cre:Girk2flox/flox mice) exhibited a clear deficit in GIRK-dependent signaling in dorsal hippocampal GABA neurons, but no evident behavioral phenotype. Mice lacking GIRK2 in forebrain pyramidal neurons (CaMKII-Cre(+):Girk2flox/flox mice) exhibited diminished GIRK-dependent signaling in dorsal, but not ventral, hippocampal pyramidal neurons. CaMKII-Cre(+):Girk2flox/flox mice also displayed a selective impairment in contextual fear conditioning, as both cue-fear and spatial learning were intact in these mice. Finally, loss of GIRK2 in forebrain pyramidal neurons correlated with enhanced long-term depression and blunted depotentiation of long-term potentiation at the Schaffer collateral/CA1 synapse in the dorsal hippocampus. Conclusions Our data suggest that GIRK channels in dorsal hippocampal pyramidal neurons are necessary for normal learning involving aversive stimuli, and support the contention that dysregulation of GIRK-dependent signaling may underlie cognitive dysfunction in some disorders.

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Effects of corticosterone on contextual fear consolidation in intact and ovariectomized female rats

Cited by 12 publications

References 42 publications

Estradiol during (analogue-) trauma: risk- or protective factor for intrusive re-experiencing?

Estradiol during (analogue-) trauma: risk- or protective factor for intrusive re-experiencing?

Effects of corticosterone on mild auditory fear conditioning and extinction; role of sex and training paradigm

G Protein-Gated K + Channel Ablation in Forebrain Pyramidal Neurons Selectively Impairs Fear Learning

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