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Cited by 224Posttraumatic Stress Disorder ResearchMemory and Neural MechanismsStress Responses and Cortisol

Effects of Single Prolonged Stress and D-Cycloserine on Contextual Fear Extinction and Hippocampal NMDA Receptor Expression in a Rat Model of PTSD

Open access
Yamamoto, Shigeto, Morinobu, Shigeru, Fuchikami, Manabu, Kurata, Akiko, Kozuru, Toshiro, Yamawaki, Shigeto·2008·Neuropsychopharmacology
DOI 10.1038/sj.npp.1301605
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Abstract

Although the impaired extinction of traumatic memory is one of the hallmark symptoms of posttraumatic stress disorder (PTSD), the underlying mechanisms of impaired extinction are unclear and effective pharmacological interventions have not yet been developed. Single prolonged stress (SPS) has been proposed as an animal model of PTSD, since rats subjected to SPS (SPS rats) show enhanced negative feedback of the HPA axis and increased contextual fear, which are characteristics similar to those observed in patients with PTSD. In this study, using SPS rats, we examined (a) the ability of SPS to impair fear extinction, (b) whether D-cycloserine (DCS) can alleviate impaired fear extinction in SPS rats, and (c) the effect of SPS and/or DCS on the levels of N-methyl-D-aspartate (NMDA) receptor subunit mRNAs in the rat hippocampus during extinction training. SPS rats exhibited impaired fear extinction in the contextual fear test, which was alleviated by the repeated administration of DCS. The effect of enhanced extinction, induced by the administration of DCS to SPS rats, was maintained for one week following extinction training. SPS induced significant upregulation of the levels of NMDA receptor subunit mRNAs before and during the period of extinction training, while repeated administration of DCS eliminated the enhanced mRNA levels of NMDARs. Behavioral analyses indicated that SPS is an appropriate animal model of PTSD and that DCS may be effective in the treatment of PTSD. These findings suggest that DCS, irrespective of its mechanistic involvement in the enhancement of fear extinction, may help to reverse hippocampal plasticity, and thus reverse the NMDA compensatory alterations.

AI snapshot

Written from the paper’s full text.

TL;DR

In a rat single prolonged stress (SPS) model of PTSD, SPS impaired contextual fear extinction and upregulated hippocampal NMDA receptor subunit mRNAs, while repeated oral D-cycloserine (DCS) alleviated the extinction deficit and reduced the elevated NMDAR mRNA levels. The authors conclude that SPS is an appropriate PTSD animal model and that DCS may help reverse hippocampal NMDA compensatory alterations, though the mechanism remains unclear.

Key findings

  • SPS rats showed impaired contextual fear extinction: freezing did not differ from Sham on day 1 (t(18)=1.54, p=0.13), but SPS rats froze significantly more on days 2–5 (day 2: t(18)=2.76, p<0.05; day 3: t(18)=3.67, p<0.01; day 4: t(18)=3.63, p<0.01; day 5: t(18)=4.11, p<0.01).
  • Repeated DCS (15 mg/kg oral, daily for 6 days) alleviated impaired fear extinction in SPS rats, and the enhanced extinction was maintained one week after the fifth extinction training without DCS; DCS did not affect consolidation of original fear on day 1.
  • In hippocampus, all four NMDAR subunit mRNAs (NR1, NR2A, NR2B, NR2C) were higher in SPS than Sham before fear conditioning and during extinction training (e.g., day 0: NR1 t(10)=5.04, p<0.01; NR2A t(10)=2.93, p<0.05; NR2B t(10)=3.68, p<0.01; NR2C t(10)=5.11, p<0.01; day 4 all p<0.01).
  • Repeated DCS eliminated the enhanced NMDAR mRNA levels in SPS rats; Experiment 4 found significant stress×drug interactions for NR1, NR2A, NR2B, and NR2C, with the reduction most consistent for the SPS group, and the discussion specifically notes DCS eliminated enhanced NR2A and NR2B mRNA levels in SPS rats.

Methods

  • Male Sprague-Dawley rats weighing 300–350 g were used; total N=176 (Experiment 1: N=20; Experiment 2: N=76; Experiment 3: N=44; Experiment 4: N=36). SPS consisted of 2 h restraint, 20 min forced swim at 24°C, ether anesthesia, then 7 days undisturbed in home cage.
  • Contextual fear conditioning used two 4-s, 0.8-mA footshocks; extinction training was 10 min of context exposure without footshock on five consecutive days. Freezing was scored blindly, with interrater reliability r=0.96.
  • DCS was administered orally in drinking water at a target dose of 15 mg/kg/day for 6 days (Experiment 2A) or 5 days (Experiment 4). Hippocampal NMDAR subunit mRNAs were measured by real-time quantitative PCR relative to GAPDH; analyses used ANOVA, t-tests, and Tukey post hoc tests, with significance at p<0.05.

Limitations

  • Stated: oral DCS administration meant the exact amount consumed by each rat daily could not be accurately confirmed, so the DCS concentration could only be assumed to be approximately 15 mg/kg.
  • Stated: the study did not evaluate NMDAR protein levels, NMDAR phosphorylation, or NMDAR-mediated intracellular signal transduction in the hippocampus.
  • Stated: enhanced hippocampal NMDA receptor expression does not necessarily occur in other brain regions, could be a consequence rather than a causative factor of impaired fear extinction, and other regions such as the amygdala and medial prefrontal cortex may be involved. Evident: DCS did not enhance extinction in Sham rats, which the authors suggest may reflect a floor effect from the 10-min context exposure or inadequate DCS consumption, and the mechanism by which DCS alleviates extinction impairment was not clarified.

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Registry

Crossref · 10.1038/sj.npp.1301605

Cites

39 of 39 references verified0 citation errors · 0 not checkable

Statistics

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Claims the paper makes

0 of 41 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    SPS rats exhibit impaired fear extinction in the contextual fear test.

    “SPS rats exhibited impaired fear extinction in the contextual fear test, which was alleviated by the repeated administration of DCS.”
    • Also stated in: § Experiment 1: Influence of SPS on Fear Extinction · plain
      “During repeated context exposure, however, a significant difference in the freezing responses between the two groups appeared on day 2, and significant differences persisted until day 5 (day 2: t(18) ¼ 2.76; po0.05, day 3: t(18) ¼ 3.67; po0.01, day 4: t(18) ¼ 3.63; po0.01, day 5: t(18) ¼ 4.11; po0.01) (Figure 2).”
    Quote in the paperSubstantial claim
  • Findingown data

    SPS induces significant upregulation of the levels of NMDA receptor subunit mRNAs in the hippocampus before and during the period of extinction training.

    “SPS induced significant upregulation of the levels of NMDA receptor subunit mRNAs before and during the period of extinction training, while repeated administration of DCS eliminated the enhanced mRNA levels of NMDARs.”
    • Also stated in: § Experiment 3: Measurement of the mRNA Levels of NMDARs in the Hippocampus During Extinction Training · boosted
      “Collectively, our comparison of NMDAR expression in the hippocampus between the SPS and Sham groups demonstrated that the levels of all four NMDAR subunits in the SPS group were significantly higher than those in the Sham group, both before and during the entire period of extinction training.”
    • Also stated in: § Experiment 3: Measurement of the mRNA Levels of NMDARs in the Hippocampus During Extinction Training · plain
      “before fear conditioning, we observed that the levels of all NMDAR subunit mRNAs in the SPS group were higher than those in the Sham group (NR 1: t(10) ¼ 5.04; po0.01,NR2A: t(10) ¼ 2.93; po0.05,NR2B: t(10) ¼ 3.68; po0.01,NR2C: t(10) ¼ 5.11; po0.01).”
    Quote in the paperSubstantial claim
  • Findingown data

    Repeated administration of DCS eliminates the enhanced mRNA levels of NMDARs in SPS rats.

    “while repeated administration of DCS eliminated the enhanced mRNA levels of NMDARs.”
    Quote in the paperSubstantial claim
  • Findingown data

    The enhanced extinction induced by DCS in SPS rats is maintained for one week following extinction training.

    “The effect of enhanced extinction, induced by the administration of DCS to SPS rats, was maintained for one week following extinction training.”
    • Also stated in: § Experiment 2: Effects of DCS Administration on Fear Extinction · plain
      “Both of the groups administered with DCS exhibited less freezing on day 12 as compared to day 5.”
    Quote in the paperSubstantial claim
  • Findingown data

    Repeated administration of DCS alleviates impaired fear extinction in SPS rats.

    “SPS rats exhibited impaired fear extinction in the contextual fear test, which was alleviated by the repeated administration of DCS.”
    • Also stated in: § Experiment 2: Effects of DCS Administration on Fear Extinction · boosted
      “In Experiment 2A, three-way repeated measures ANOVA demonstrated significant main effects of day (F(4, 72) ¼ 105.39, po0.01), stress (F(1, 18) ¼ 16.41, po0.01), drug (F(1, 18) ¼ 9.81, po0.01), and significant interactions between stress and drug (F(1, 18) ¼ 5.71, po0.05), and between stress and day (F(4, 72) ¼ 2.71, po0.05).”
    Quote in the paperSubstantial claim
  • The quote only partly states this claim. 2
  • Classified as probably not a substantial claim. 23
  • May combine two claims. 8

  • The quote only partly states this claim.

    Findingown data

    Repeated administration of DCS eliminated the enhanced mRNA levels of NR2A and NR2B in SPS rats.

    “in Experiment 4, we also found that the administration of DCS eliminated the enhanced mRNA levels of NR2A and NR2B in SPS rats.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

    Study design and conductown data

    DCS intake was verified by measuring daily water consumption.

    “We also verified that the three rats in any one cage consumed approximately 120 ml of Milli-Q water, with or without DCS.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All standards and samples were assayed in triplicate.

    “All standards and samples were assayed in triplicate.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    In Experiment 4, rats showed freezing responses similarly to comparable rats in Experiment 2A despite independent sets of rats being used.

    “Rats showed freezing responses similarly to comparable rats in Experiment 2A.This was despite independent sets of rats being used for each experiment.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Enhanced NMDA receptor expression in the hippocampus does not mean the same is happening in other areas of brain.

    “Third, it should be noted that because there is enhanced NMDA receptor expression in the hippocampus, this does not mean that the same is happening in other areas of brain.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    It was not possible to accurately confirm the amount of Milli-Q water consumed by each rat daily.

    “However, using this methodology it was not possible to accurately confirm the amount of Milli-Q water consumed by each rat daily.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    The DCS dose (15 mg/kg per rat) was chosen on the basis of other behavioral studies.

    “The DCS dose (15 mg/kg per rat) was chosen on the basis of the results of other behavioral studies (Ledgerwood et al, 2003(Ledgerwood et al, , 2005;;Walker et al, 2002).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Ledgerwood et al, 2003 source

      Not checked in the free run.

    • cites Ledgerwood et al, 2005

      Not checked in the free run.

    • cites Walker et al, 2002 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    We did not evaluate changes in the protein level of NMDARs, the extent of NMDAR phosphorylation, or intracellular signal transduction mediated by NMDARs in the hippocampus.

    “Second, we did not evaluate changes in the protein level of NMDARs, the extent of NMDAR phosphorylation, or intracellular signal transduction mediated by NMDARs in the hippocampus.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    DCS enhanced extinction rather than consolidation of fear.

    “Subsequently, DCS was found to enhance extinction, rather than consolidation of fear.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The interrater reliability between the two scorers was high (r = 0.96).

    “The interrater reliability between the two scorers was high (r ¼ 0.96).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Intrahippocampal infusions of AP5 immediately after the first of four daily extinction exposures produce a lasting impairment that persists even with additional extinction training without infusions.

    “For example, Szapiro et al (2003), using a step-down avoidance paradigm, found that intrahippocampal infusions (CA1 region) of the NMDA receptor antagonist, AP5, immediately after the first of four daily extinction exposures, produced a lasting impairment that persisted even with additional extinction training without infusions.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Szapiro et al, 2003

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Brain regions such as the hippocampus, amygdala, and prefrontal cortex are involved in memory extinction.

    “Although the neurocircuitry mechanism of contextual fear extinction is not fully understood, brain regions such as the hippocampus, amygdala, and prefrontal cortex are involved in the memory extinction (Sotres-Bayon et al, 2004, 2006).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Sotres-Bayon et al, 2004, 2006

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    DCS may help to reverse hippocampal plasticity, and thus reverse the NMDA compensatory alterations.

    “These findings suggest that DCS, irrespective of its mechanistic involvement in the enhancement of fear extinction, may help to reverse hippocampal plasticity, and thus reverse the NMDA compensatory alterations.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The levels of NMDAR subunit mRNAs measured by RT-PCR reflect hippocampal NMDA receptor expression or function.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All animal procedures were conducted in strict accordance with the Hiroshima University School of Medicine Animal Care Committee Guiding Principles.

    “All animal procedures were conducted in strict accordance with the Hiroshima University School of Medicine Animal Care Committee Guiding Principles”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Animals were randomly assigned to experimental groups.

    “Animals were randomly assigned to two groups (SPS, Sham).”
    • Also stated in: § Drug Treatment · plain
      “Animals were randomly assigned to four groups (SPS, SPS + DCS, Sham, Sham + DCS).”
    • Also stated in: § Measurement of the Levels of NMDARs in the Hippocampus by Real-Time Quantitative Polymerase Chain Reaction (RT-PCR) · plain
      “Animals were randomly assigned to two groups (SPS, Sham), and were sacrificed by decapitation at the indicated time on day 0 (before fear conditioning), on day 1 (after the first context exposure), or on day 4 (after the fourth context exposure).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Studies by Parnas et al (2005) and Quartermain et al (1994) described multiple administration of DCS before fear conditioning or the maze learning test, respectively.

    “Studies reported by Parnas et al (2005) and Quartermain et al (1994) described the multiple administration of DCS before fear conditioning or the maze learning test, respectively (ie preadministration of DCS).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Parnas et al (2005)

      Not checked in the free run.

    • cites Quartermain et al (1994) source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The hippocampus has strong reciprocal connections with the mPFC and the amygdala; these three brain regions seem to interactively coordinate the encoding and expression of fear extinction.

    “The hippocampus has strong reciprocal connections with the mPFC and the amygdala; these three brain regions seem to interactively coordinate the encoding and expression of fear extinction (Sotres-Bayon et al, 2006).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Sotres-Bayon et al, 2006 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Chronic preexposure of DCS eliminates effects upon fear extinction.

    “On the other hand, chronic preexposure of DCS has been reported to eliminate effects upon fear extinction (Parnas et al, 2005).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Parnas et al, 2005

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Muscimol inactivation of the dorsal hippocampus reduced the rate of extinction and prevented the context dependency of extinction.

    “For example, Corcoran et al (2005) have demonstrated that muscimol inactivation of the dorsal hippocampus reduced the rate of extinction and prevented the context dependency of extinction.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Corcoran et al (2005)

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Treating the dorsal hippocampus with muscimol produced selective impairment in the context specificity of extinction.

    “Previous studies by this group indicated that treating the dorsal hippocampus with muscimol produced selective impairment in the context specificity of extinction (Corcoran and Maren, 2001).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Corcoran and Maren, 2001

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Hippocampal expression of BDNF is required for the neural plasticity underlying the acquisition or consolidation of extinction memories.

    “More recently, Heldt et al (2007) demonstrated that the hippocampal expression of BDNF is required for the neural plasticity underlying the acquisition or consolidation of extinction memories.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Heldt et al (2007) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Heresco-Levy et al (2002) used daily chronic dosing without exposure therapy, while Hofmann et al (2006) and Ressler et al (2004) used acute dosing with exposure therapy.

    “Heresco-Levy et al (2002) used daily chronic dosing without exposure therapy, while Hofmann et al (2006) and Ressler et al (2004) used acute dosing with exposure therapy.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Heresco-Levy et al (2002)

      Not checked in the free run.

    • cites Hofmann et al (2006) source

      Not checked in the free run.

    • cites Ressler et al (2004) source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Structural plasticity involving actin rearrangement within dorsal hippocampus is required for contextual fear extinction.

    “In addition, Fischer et al (2004) have shown that structural plasticity involving actin rearrangement within dorsal hippocampus is required for contextual fear extinction.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Fischer et al (2004)

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    We cannot rule out the possibility of the involvement of other brain regions in fear extinction.

    “Finally, we cannot rule out the possibility of the involvement of other brain regions in fear extinction as described above.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    DCS facilitated NMDAR-mediated signal transduction and synaptic plasticity in the CA1 field of rat hippocampal slices.

    “For example, Rouaud and Billard (2003) showed that DCS facilitated NMDAR-mediated signal transduction and synaptic plasticity in the CA1 field of rat hippocampal slices.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Rouaud and Billard (2003)

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    In our study, we did not clarify the mechanism by which DCS alleviated the impairment of extinction in SPS rats.

    “In our study, we did not clarify the mechanism by which DCS alleviated the impairment of extinction in SPS rats.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Study design and conductnone given

    It is plausible that the enhanced NMDA receptor expression observed in the hippocampus could be a consequence, but not a causative factor, of impaired fear extinction.

    “In addition, it is plausible that the enhanced NMDA receptor expression observed in the hippocampus could be a consequence, but not a causative factor, of impaired fear extinction.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Chronic preexposure to DCS for 15 days led to a significant decrease in the effect of DCS upon the maze learning test.

    “Similarly, Quartermain et al (1994) reported that chronic preexposure to DCS for 15 days led to a significant decrease in the effect of DCS upon the maze learning test (Quartermain et al, 1994).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Quartermain et al (1994) source

      Not checked in the free run.

28 of 28

  • The paper relies on this without support.

    DCS enhances excitatory neurotransmission mediated by NMDA receptors by binding to the strychnine-insensitive glycine recognition site of the NMDA receptor complex, without inducing neurotoxicity.

    “DCS enhances excitatory neurotransmission mediated by NMDA receptors, by binding to the strychnine-insensitive glycine recognition site of the NMDA receptor complex, without inducing neurotoxicity.”

  • The paper relies on this without support.

    The levels of NMDAR subunit mRNAs measured by RT-PCR reflect hippocampal NMDA receptor expression or function.

    “To elucidate whether the hippocampal glutamatergic systems are involved in fear extinction, we used RT-PCR to measure alterations in NMDAR mRNA levels in the hippocampus during extinction training (Experiment 3).”

  • The authors state this as an assumption.

    The concentration of DCS could only be assumed to be approximately 15 mg/kg.

    “Hence, it should be noted that the concentration of DCS could only be assumed to be approximately 15 mg/kg.”

  • The paper relies on this without support.

    This is the first study indicating the efficacy of DCS upon fear extinction in a conditioned stress model of PTSD.

    “This is the first study indicating the efficacy of DCS upon fear extinction in a conditioned stress model of PTSD.”

  • The paper relies on this without support.

    Little has been reported previously concerning the effects of DCS upon fear consolidation.

    “To our knowledge, little has been reported previously concerning the effects of DCS upon fear consolidation.”

  • The paper relies on this without support.

    The initial level of freezing is critical in the assessment of contextual fear extinction by DCS.

    “As mentioned above, the initial level of freezing is also critical in the assessment of contextual fear extinction by DCS.”
6 of 6

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Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Experiment 2B ANOVA degrees of freedom conflict with group sizes

    Major

    Figure 4 reports nine rats in each of four groups, or 36 rats total, which would give 32 between-subject degrees of freedom. The reported ANOVA uses 16, consistent with only 20 rats.

  • Experiment 2A ANOVA degrees of freedom conflict with group sizes

    Minor

    Figure 3 reports four groups of 10 rats, or 40 rats total; its day-1 ANOVA also uses a residual degree of freedom of 36. The reported three-way repeated-measures ANOVA instead uses 18 between-subject degrees of freedom, consistent with only 20 rats.

  • Rat weights are given in both grams and milligrams

    Minor

    The animals are described as weighing 300-350 g, but the dosing calculation gives an average rat weight of 330 mg. These values differ by a factor of 1,000.

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Related

Authors
Yamamoto, S., Morinobu, S., Fuchikami, M., Kurata, A., Kozuru, T., & Yamawaki, S.
Affiliations
Hiroshima University (JP)
Corresponding author
Yamawaki, Shigeto
ORCID
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2007-10-24
Volume
33
Issue
9
Pages
2108-2116
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/sj.npp.1301605
OpenAlex
W2060475258
Cited by
224
References
39
Citations by year
2026: 2 · 2025: 9 · 2024: 3 · 2023: 11 · 2022: 7 · 2021: 11 · 2020: 15 · 2019: 13 · 2018: 23 · 2017: 12 · 2016: 13 · 2015: 16 · 2014: 16 · 2013: 18 · 2012: 17
FWCI
9.10
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Neuropsychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion)
  • Hiroshima University Institutional Repository (submittedVersion, other-oa)
  • Hiroshima University Acedemic Information Repository (Hiroshima University) (submittedVersion)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
post-traumatic stress disorder, single prolonged stress, D-cycloserine, fear extinction, contextual fear, NMDA receptor subunits, hippocampus, hippocampal plasticity, hypothalamic-pituitary-adrenal axis, animal model of PTSD
MeSH terms
Analysis of Variance, Animals, Antimetabolites, Behavior, Animal, Cycloserine, Disease Models, Animal, Electroshock, Extinction, Psychological, Fear, Gene Expression Regulation, Hippocampus, Male, RNA, Messenger, Stress Disorders, Post-Traumatic, Stress, Psychological, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Rats

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