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2000
Volume 24, Issue 2
  • ISSN: 1570-159X
  • E-ISSN: 1875-6190

Abstract

Post-traumatic stress disorder (PTSD) represents a grave and expansive mental illness, caused by experiencing or witnessing traumatic events that invoke profound feelings of helplessness, fear and anxiety. Reflecting the clinical features of PTSD, the single prolonged stress (SPS) model in rodents was developed to elucidate the pathogenesis and identify potential therapeutic interventions. This review aimed to deepen our understanding of the mechanisms and therapeutic methods for PTSD. We conducted a comprehensive literature search on PubMed and Web of Science using keywords such as “SPS”, “PTSD”, and “mechanisms”. Clinical and animal research, especially the exploration of the mechanisms and treatments, were included in this review. We identified a total of 327 articles. After removing duplicates and screening the full texts, we selected only 137 articles. Based on the literature, we examined the parallels and divergences between PTSD and the SPS model regarding symptomatic manifestations, affected brain regions, and molecular markers, demonstrating that the SPS model can effectively replicate PTSD-like behaviors in rodents. Guided by clinical research findings, we further synthesized the mechanisms by which SPS induces PTSD, focusing on the modulation of relevant signaling pathways and neural circuits. Additionally, we reviewed potential intervention strategies for PTSD using this model, encompassing both pharmacological and non-pharmacological therapies. This review offers significant implications for basic research rooted in the clinical characteristics of PTSD, suggesting that studies utilizing the SPS model could enhance our understanding of PTSD and aid in the identification of effective treatment strategies.

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References

  1. ResslerK.J. BerrettaS. BolshakovV.Y. RossoI.M. MeloniE.G. RauchS.L. CarlezonW.A. Post-traumatic stress disorder: Clinical and translational neuroscience from cells to circuits.Nat. Rev. Neurol.202218527328810.1038/s41582‑022‑00635‑8 35352034
     [Google Scholar]
  2. ThakurA. ChoudharyD. KumarB. ChaudharyA. A review on post-traumatic stress disorder (PTSD): Symptoms, therapies and recent case studies.Curr. Mol. Pharmacol.202215350251610.2174/1874467214666210525160944 34036925
     [Google Scholar]
  3. MeriansA.N. SpillerT. Harpaz-RotemI. KrystalJ.H. PietrzakR.H. Post-traumatic stress disorder.Med. Clin. North Am.20231071859910.1016/j.mcna.2022.04.003 36402502
     [Google Scholar]
  4. BissonJ.I. OlffM. Prevention and treatment of PTSD: The current evidence base.Eur. J. Psychotraumatol.2021121182438110.1080/20008198.2020.1824381 34992739
     [Google Scholar]
  5. TörökB. SiposE. PivacN. ZelenaD. Modelling posttraumatic stress disorders in animals.Prog. Neuropsychopharmacol. Biol. Psychiatry20199011713310.1016/j.pnpbp.2018.11.013 30468906
     [Google Scholar]
  6. BoutonM.E. MarenS. McNallyG.P. Behavioral and neurobiological mechanisms of pavlovian and instrumental extinction learning.Physiol. Rev.2021101261168110.1152/physrev.00016.2020 32970967
     [Google Scholar]
  7. DawsS.E. JamiesonS. de NijsL. JonesM. SnijdersC. KlengelT. JosephN.F. KrauskopfJ. KleinjansJ. VinkersC.H. BoksM.P.M. GeuzeE. VermettenE. BerrettaS. ResslerK.J. RuttenB.P.F. RumbaughG. MillerC.A. MicroRNA regulation of persistent stress-enhanced memory.Mol. Psychiatry202025596597610.1038/s41380‑019‑0432‑2 31142820
     [Google Scholar]
  8. Van AsscheI.A. PadillaM.S. StupartO.S.R.P. MiltonA.L. Refinement of the stress-enhanced fear learning model of post-traumatic stress disorder: A behavioral and molecular analysis.Lab Anim. (NY)2022511129330010.1038/s41684‑022‑01054‑4 36266512
     [Google Scholar]
  9. AdamecR. HolmesA. BlundellJ. Vulnerability to lasting anxiogenic effects of brief exposure to predator stimuli: Sex, serotonin and other factors—Relevance to PTSD.Neurosci. Biobehav. Rev.20083271287129210.1016/j.neubiorev.2008.05.005 18550167
     [Google Scholar]
  10. SchönerJ. HeinzA. EndresM. GertzK. KronenbergG. Post‐traumatic stress disorder and beyond: An overview of rodent stress models.J. Cell. Mol. Med.201721102248225610.1111/jcmm.13161 28374949
     [Google Scholar]
  11. LiberzonI. KrstovM. YoungE.A. Stress-restress: Effects on ACTH and fast feedback.Psychoneuroendocrinology199722644345310.1016/S0306‑4530(97)00044‑9 9364622
     [Google Scholar]
  12. LiberzonI. YoungE.A. Effects of stress and glucocorticoids on CNS oxytocin receptor binding.Psychoneuroendocrinology199722641142210.1016/S0306‑4530(97)00045‑0 9364620
     [Google Scholar]
  13. CathomasF. MurroughJ.W. NestlerE.J. HanM.H. RussoS.J. Neurobiology of resilience: Interface between mind and body.Biol. Psychiatry201986641042010.1016/j.biopsych.2019.04.011 31178098
     [Google Scholar]
  14. AlmeidaF.B. PinnaG. BarrosH.M.T. The role of HPA axis and allopregnanolone on the neurobiology of major depressive disorders and PTSD.Int. J. Mol. Sci.20212211549510.3390/ijms22115495 34071053
     [Google Scholar]
  15. WangJ. GaoF. CuiS. YangS. GaoF. WangX. ZhuG. Utility of 7,8-dihydroxyflavone in preventing astrocytic and synaptic deficits in the hippocampus elicited by PTSD.Pharmacol. Res.202217610607910.1016/j.phrs.2022.106079 35026406
     [Google Scholar]
  16. ZhangZ. SongZ. ShenF. XieP. WangJ. ZhuA. ZhuG. Ginsenoside Rg1 prevents PTSD-like behaviors in mice through promoting synaptic proteins, reducing Kir4.1 and TNF-α in the Hippocampus.Mol. Neurobiol.20215841550156310.1007/s12035‑020‑02213‑9 33215390
     [Google Scholar]
  17. JiM. ZhangZ. GaoF. YangS. WangJ. WangX. ZhuG. Curculigoside rescues hippocampal synaptic deficits elicited by PTSD through activating cAMP‐PKA signaling.Phytother. Res.202337275977310.1002/ptr.7658 36200803
     [Google Scholar]
  18. Maples-KellerJ. WatkinsL.E. NylocksK.M. YasinskiC. CoghlanC. BlackK. JovanovicT. RauchS.A.M. RothbaumB.O. NorrholmS.D. Acquisition, extinction, and return of fear in veterans in intensive outpatient prolonged exposure therapy: A fear-potentiated startle study.Behav. Res. Ther.202215410412410.1016/j.brat.2022.104124 35642990
     [Google Scholar]
  19. NahumK. TodderD. ZoharJ. CohenH. The role of microglia in the (Mal)adaptive response to traumatic experience in an animal model of PTSD.Int. J. Mol. Sci.20222313718510.3390/ijms23137185 35806185
     [Google Scholar]
  20. GermainA. BuysseD.J. NofzingerE. Sleep-specific mechanisms underlying posttraumatic stress disorder: Integrative review and neurobiological hypotheses.Sleep Med. Rev.200812318519510.1016/j.smrv.2007.09.003 17997114
     [Google Scholar]
  21. ClarkJ.W. DaykinH. MethaJ.A. AlloccaG. HoyerD. DrummondS.P.A. JacobsonL.H. Manipulation of rapid eye movement sleep via orexin and GABAA receptor modulators differentially affects fear extinction in mice: Effect of stable versus disrupted circadian rhythm.Sleep2021449zsab06810.1093/sleep/zsab068 33720375
     [Google Scholar]
  22. BallT.M. GunaydinL.A. Measuring maladaptive avoidance: From animal models to clinical anxiety.Neuropsychopharmacology202247597898610.1038/s41386‑021‑01263‑4 35034097
     [Google Scholar]
  23. YangS. QuY. WangJ. GaoF. JiM. XieP. ZhuA. TanB. WangX. ZhuG. Anshen Dingzhi prescription in the treatment of PTSD in mice: Investigation of the underlying mechanism from the perspective of hippocampal synaptic function.Phytomedicine202210115413910.1016/j.phymed.2022.154139 35523115
     [Google Scholar]
  24. XieP. ChenL. WangJ. WangX. YangS. ZhuG. Polysaccharides from Polygonatum cyrtonema Hua prevent post-traumatic stress disorder behaviors in mice: Mechanisms from the perspective of synaptic injury, oxidative stress, and neuroinflammation.J. Ethnopharmacol.2024319Pt 111716510.1016/j.jep.2023.117165 37696440
     [Google Scholar]
  25. RautS.B. MaratheP.A. van EijkL. EriR. RavindranM. BenedekD.M. UrsanoR.J. CanalesJ.J. JohnsonL.R. Diverse therapeutic developments for post-traumatic stress disorder (PTSD) indicate common mechanisms of memory modulation.Pharmacol. Ther.202223910819510.1016/j.pharmthera.2022.108195 35489438
     [Google Scholar]
  26. DingX. YangM. WuN. LiJ. SongR. Blockade of dopamine D3 receptor in ventral tegmental area attenuating contextual fear memory.Biomed. Pharmacother.202315811417910.1016/j.biopha.2022.114179 36592493
     [Google Scholar]
  27. VanderheydenW.M. LeftonM. FloresC.C. OwadaY. GerstnerJ.R. Fabp7 is required for normal sleep suppression and anxiety-associated phenotype following single-prolonged stress in mice.Neuroglia202232738310.3390/neuroglia3020005 36909794
     [Google Scholar]
  28. SouzaR.R. NobleL.J. McIntyreC.K. Using the single prolonged stress model to examine the pathophysiology of PTSD.Front. Pharmacol.2017861510.3389/fphar.2017.00615 28955225
     [Google Scholar]
  29. StanderV.A. ThomsenC.J. Highfill-McRoyR.M. Etiology of depression comorbidity in combat-related PTSD: A review of the literature.Clin. Psychol. Rev.2014342879810.1016/j.cpr.2013.12.002 24486520
     [Google Scholar]
  30. Della ValleR. MohammadmirzaeiN. KnoxD. Single prolonged stress alters neural activation in the periacqueductal gray and midline thalamic nuclei during emotional learning and memory.Learn. Mem.2019261040341110.1101/lm.050310.119 31527186
     [Google Scholar]
  31. DeslauriersJ. TothM. Der-AvakianA. RisbroughV.B. Current status of animal models of posttraumatic stress disorder: Behavioral and biological phenotypes, and future challenges in improving translation.Biol. Psychiatry2018831089590710.1016/j.biopsych.2017.11.019 29338843
     [Google Scholar]
  32. HarnettN.G. GoodmanA.M. KnightD.C. PTSD-related neuroimaging abnormalities in brain function, structure, and biochemistry.Exp. Neurol.202033011333110.1016/j.expneurol.2020.113331 32343956
     [Google Scholar]
  33. FaniN. KingT.Z. ShinJ. SrivastavaA. BrewsterR.C. JovanovicT. BradleyB. ResslerK.J. Structural and functional connectivity in posttraumatic stress disorder: Associations with FKBP5.Depress. Anxiety201633430030710.1002/da.22483 27038411
     [Google Scholar]
  34. HarnettN.G. FerenceE.W. KnightA.J. KnightD.C. White matter microstructure varies with post-traumatic stress severity following medical trauma.Brain Imaging Behav.20201441012102410.1007/s11682‑018‑9995‑9 30519996
     [Google Scholar]
  35. YehudaR. HogeC.W. McFarlaneA.C. VermettenE. LaniusR.A. NievergeltC.M. HobfollS.E. KoenenK.C. NeylanT.C. HymanS.E. Post-traumatic stress disorder.Nat. Rev. Dis. Primers2015111505710.1038/nrdp.2015.57 27189040
     [Google Scholar]
  36. AchesonD.T. GresackJ.E. RisbroughV.B. Hippocampal dysfunction effects on context memory: Possible etiology for posttraumatic stress disorder.Neuropharmacology201262267468510.1016/j.neuropharm.2011.04.029 21596050
     [Google Scholar]
  37. ClancyK.J. DevignesQ. KumarP. MayV. HammackS.E. AkmanE. CasteenE.J. PerniaC.D. JobsonS.A. LewisM.W. DaskalakisN.P. CarlezonW.A. ResslerK.J. RauchS.L. RossoI.M. Circulating PACAP levels are associated with increased amygdala-default mode network resting-state connectivity in posttraumatic stress disorder.Neuropsychopharmacology20234881245125410.1038/s41386‑023‑01593‑5 37161077
     [Google Scholar]
  38. BryantR.A. FelminghamK.L. MalhiG. AndrewE. KorgaonkarM.S. The distinctive neural circuitry of complex posttraumatic stress disorder during threat processing.Psychol. Med.20215171121112810.1017/S0033291719003921 31910918
     [Google Scholar]
  39. LaniusR.A. BluhmR. LaniusU. PainC. A review of neuroimaging studies in PTSD: Heterogeneity of response to symptom provocation.J. Psychiatr. Res.200640870972910.1016/j.jpsychires.2005.07.007 16214172
     [Google Scholar]
  40. NicholsonA.A. DensmoreM. FrewenP.A. ThébergeJ. NeufeldR.W.J. McKinnonM.C. LaniusR.A. The dissociative subtype of posttraumatic stress disorder: Unique resting-state functional connectivity of basolateral and centromedial amygdala complexes.Neuropsychopharmacology201540102317232610.1038/npp.2015.79 25790021
     [Google Scholar]
  41. ZoladzP.R. DiamondD.M. Current status on behavioral and biological markers of PTSD: A search for clarity in a conflicting literature.Neurosci. Biobehav. Rev.201337586089510.1016/j.neubiorev.2013.03.024 23567521
     [Google Scholar]
  42. LeeB. PothulaS. WuM. KangH. GirgentiM.J. PicciottoM.R. DiLeoneR.J. TaylorJ.R. DumanR.S. Positive modulation of N-methyl-D-aspartate receptors in the mPFC reduces the spontaneous recovery of fear.Mol. Psychiatry20222752580258910.1038/s41380‑022‑01498‑7 35418600
     [Google Scholar]
  43. XiaoS. YangZ. SuT. GongJ. HuangL. WangY. Functional and structural brain abnormalities in posttraumatic stress disorder: A multimodal meta-analysis of neuroimaging studies.J. Psychiatr. Res.202215515316210.1016/j.jpsychires.2022.08.010 36029627
     [Google Scholar]
  44. DomitrovicS.S. NikolacP.M. UzunS. NedicE.G. KozumplikO. SvobS.D. MimicaN. PivacN. Reduced plasma BDNF concentration and cognitive decline in veterans with PTSD.Psychiatry Res.202231611477210.1016/j.psychres.2022.114772 35961151
     [Google Scholar]
  45. PetersJ. Dieppa-PereaL.M. MelendezL.M. QuirkG.J. Induction of fear extinction with hippocampal-infralimbic BDNF.Science201032859831288129010.1126/science.1186909 20522777
     [Google Scholar]
  46. KozlovskyN. MatarM.A. KaplanZ. KotlerM. ZoharJ. CohenH. Long-term down-regulation of BDNF mRNA in rat hippocampal CA1 subregion correlates with PTSD-like behavioural stress response.Int. J. Neuropsychopharmacol.200710674175810.1017/S1461145707007560 17291374
     [Google Scholar]
  47. TakeiS. MorinobuS. YamamotoS. FuchikamiM. MatsumotoT. YamawakiS. Enhanced hippocampal BDNF/TrkB signaling in response to fear conditioning in an animal model of posttraumatic stress disorder.J. Psychiatr. Res.201145446046810.1016/j.jpsychires.2010.08.009 20863519
     [Google Scholar]
  48. YinJ.B. LiuH.X. ShiW. DingT. HuH.Q. GuoH.W. JinS. WangX.L. ZhangT. LuY.C. CaoB.Z. Various BDNF administrations attenuate SPS-induced anxiety-like behaviors.Neurosci. Lett.202278813685110.1016/j.neulet.2022.136851 36007708
     [Google Scholar]
  49. PassosI.C. Vasconcelos-MorenoM.P. CostaL.G. KunzM. BrietzkeE. QuevedoJ. SalumG. MagalhãesP.V. KapczinskiF. Kauer-Sant’AnnaM. Inflammatory markers in post-traumatic stress disorder: A systematic review, meta-analysis, and meta-regression.Lancet Psychiatry20152111002101210.1016/S2215‑0366(15)00309‑0 26544749
     [Google Scholar]
  50. ImaiR. HoriH. ItohM. LinM. NiwaM. InoK. OgawaS. IshidaM. SekiguchiA. MatsuiM. KunugiH. AkechiT. KamoT. KimY. Inflammatory markers and their possible effects on cognitive function in women with posttraumatic stress disorder.J. Psychiatr. Res.201810219220010.1016/j.jpsychires.2018.04.009 29684628
     [Google Scholar]
  51. DaskalakisN.P. CohenH. NievergeltC.M. BakerD.G. BuxbaumJ.D. RussoS.J. YehudaR. New translational perspectives for blood-based biomarkers of PTSD: From glucocorticoid to immune mediators of stress susceptibility. Exp. Neurol.,2016284Pt B13314010.1016/j.expneurol.2016.07.024
     [Google Scholar]
  52. HendricksonR.C. RaskindM.A. Noradrenergic dysregulation in the pathophysiology of PTSD. Exp. Neurol.,2016284Pt B18119510.1016/j.expneurol.2016.05.014 27222130
     [Google Scholar]
  53. YahyaviS.T. ZarghamiM. NaghshvarF. DaneshA. Relationship of cortisol, norepinephrine, and epinephrine levels with war-induced posttraumatic stress disorder in fathers and their offspring.Rev. Bras. Psiquiatr.2015372939810.1590/1516‑4446‑2014‑1414 26083811
     [Google Scholar]
  54. DelahantyD.L. RaimondeA.J. SpoonsterE. Initial posttraumatic urinary cortisol levels predict subsequent PTSD symptoms in motor vehicle accident victims.Biol. Psychiatry200048994094710.1016/S0006‑3223(00)00896‑9 11074232
     [Google Scholar]
  55. AgorastosA. KellnerM. BakerD.G. OtteC. When time stands still.Curr. Opin. Psychiatry201427538539210.1097/YCO.0000000000000079 25023884
     [Google Scholar]
  56. MellmanT.A. BustamanteV. FinsA.I. PigeonW.R. NolanB. REM sleep and the early development of posttraumatic stress disorder.Am. J. Psychiatry2002159101696170110.1176/appi.ajp.159.10.1696 12359675
     [Google Scholar]
  57. HamB.J. CheyJ. YoonS.J. SungY. JeongD.U. Ju KimS. SimM.E. ChoiN. ChoiI.G. RenshawP.F. LyooI.K. Decreased N‐acetyl‐aspartate levels in anterior cingulate and hippocampus in subjects with post‐traumatic stress disorder: A proton magnetic resonance spectroscopy study.Eur. J. Neurosci.200725132432910.1111/j.1460‑9568.2006.05253.x 17241294
     [Google Scholar]
  58. KnoxD. PerrineS.A. GeorgeS.A. GallowayM.P. LiberzonI. Single prolonged stress decreases glutamate, glutamine, and creatine concentrations in the rat medial prefrontal cortex.Neurosci. Lett.20104801162010.1016/j.neulet.2010.05.052 20546834
     [Google Scholar]
  59. ChenS. LinZ. TanK.L. ChenR. SuW. ZhaoH. TanQ. TanW. Enhanced contextual fear memory and elevated astroglial glutamate synthase activity in hippocampal CA1 BChE shRNA knockdown mice.Front. Psychiatry20201156484310.3389/fpsyt.2020.564843 33061920
     [Google Scholar]
  60. FumagalliF. PasiniM. FrascaA. DragoF. RacagniG. RivaM.A. Prenatal stress alters glutamatergic system responsiveness in adult rat prefrontal cortex.J. Neurochem.200910961733174410.1111/j.1471‑4159.2009.06088.x 19383086
     [Google Scholar]
  61. OusdalO.T. MildeA.M. CravenA.R. ErslandL. EndestadT. MelinderA. HuysQ.J. HugdahlK. Prefrontal glutamate levels predict altered amygdala–prefrontal connectivity in traumatized youths.Psychol. Med.201949111822183010.1017/S0033291718002519 30223909
     [Google Scholar]
  62. SuX. XiaC. WangW. SunH. TanQ. ZhangS. LiL. KempG.J. YueQ. GongQ. Abnormal metabolite concentrations and amygdala volume in patients with recent-onset posttraumatic stress disorder.J. Affect. Disord.201824153954510.1016/j.jad.2018.08.018 30153637
     [Google Scholar]
  63. McDonaldA.J. MottD.D. Functional neuroanatomy of amygdalohippocampal interconnections and their role in learning and memory.J. Neurosci. Res.201795379782010.1002/jnr.23709 26876924
     [Google Scholar]
  64. FangQ. LiZ. HuangG.D. ZhangH.H. ChenY.Y. ZhangL.B. DingZ.B. ShiJ. LuL. YangJ.L. Traumatic stress produces distinct activations of GABAergic and glutamatergic neurons in Amygdala.Front. Neurosci.20181238710.3389/fnins.2018.00387 30186100
     [Google Scholar]
  65. MisakiM. MulyanaB. ZotevV. WurfelB.E. KruegerF. FeldnerM. BodurkaJ. Hippocampal volume recovery with real-time functional MRI amygdala neurofeedback emotional training for posttraumatic stress disorder.J. Affect. Disord.202128322923510.1016/j.jad.2021.01.058 33561804
     [Google Scholar]
  66. FragkakiI. ThomaesK. SijbrandijM. Posttraumatic stress disorder under ongoing threat: A review of neurobiological and neuroendocrine findings.Eur. J. Psychotraumatol.2016713091510.3402/ejpt.v7.30915 27511448
     [Google Scholar]
  67. NelsonM.D. TumpapA.M. Posttraumatic stress disorder symptom severity is associated with left hippocampal volume reduction: A meta-analytic study.CNS Spectr.201722436337210.1017/S1092852916000833 27989265
     [Google Scholar]
  68. SmithB.M. ThomassonM. YangY.C. SibertC. StoccoA. When fear shrinks the brain: A computational model of the effects of posttraumatic stress on hippocampal volume.Top. Cogn. Sci.202113349951410.1111/tops.12537 34174028
     [Google Scholar]
  69. PerrineS.A. EagleA.L. GeorgeS.A. MuloK. KohlerR.J. GerardJ. HarutyunyanA. HoolS.M. SusickL.L. SchneiderB.L. GhoddoussiF. GallowayM.P. LiberzonI. ContiA.C. Severe, multimodal stress exposure induces PTSD-like characteristics in a mouse model of single prolonged stress.Behav. Brain Res.201630322823710.1016/j.bbr.2016.01.056 26821287
     [Google Scholar]
  70. MatsumotoY. MorinobuS. YamamotoS. MatsumotoT. TakeiS. FujitaY. YamawakiS. Vorinostat ameliorates impaired fear extinction possibly via the hippocampal NMDA-CaMKII pathway in an animal model of posttraumatic stress disorder.Psychopharmacology20132291516210.1007/s00213‑013‑3078‑9 23584669
     [Google Scholar]
  71. LiuF. YangL. SunX. ZhangH. PanW. WangX. YangJ. JiM. YuanH. NOX2 mediated-parvalbumin interneuron loss might contribute to anxiety-like and enhanced fear learning behavior in a rat model of post-traumatic stress disorder.Mol. Neurobiol.201653106680668910.1007/s12035‑015‑9571‑x 26650043
     [Google Scholar]
  72. MurrayS.L. HoltonK.F. Post-traumatic stress disorder may set the neurobiological stage for eating disorders: A focus on glutamatergic dysfunction.Appetite202116710559910.1016/j.appet.2021.105599 34271078
     [Google Scholar]
  73. PittengerC. DumanR.S. Stress, depression, and neuroplasticity: A convergence of mechanisms.Neuropsychopharmacology20083318810910.1038/sj.npp.1301574 17851537
     [Google Scholar]
  74. YangS. HuJ. ChenY. ZhangZ. WangJ. ZhuG. DCC, a potential target for controlling fear memory extinction and hippocampal LTP in male mice receiving single prolonged stress.Neurobiol. Stress20243210066610.1016/j.ynstr.2024.100666 39224830
     [Google Scholar]
  75. SunJ. JiaK. SunM. ZhangX. ChenJ. ZhuG. LiC. LianB. DuZ. SunH. SunL. The GluA1-related BDNF pathway is involved in PTSD-induced cognitive flexibility deficit in attentional set-shifting tasks of rats.J. Clin. Med.20221122682410.3390/jcm11226824 36431303
     [Google Scholar]
  76. LeeB. SurB. OhS. Neuroprotective effect of Korean Red Ginseng against single prolonged stress-induced memory impairments and inflammation in the rat brain associated with BDNF expression.J. Ginseng Res.202246343544310.1016/j.jgr.2021.08.002 35600771
     [Google Scholar]
  77. EhrlichI. KleinM. RumpelS. MalinowR. PSD-95 is required for activity-driven synapse stabilization.Proc. Natl. Acad. Sci. USA2007104104176418110.1073/pnas.0609307104 17360496
     [Google Scholar]
  78. ZhangL. DengL. MaC. ZhangH. DangY. Brain-Derived neurotrophic factor delivered intranasally relieves post-traumatic stress disorder symptoms caused by a single prolonged stress in rats.Neuropsychobiology2023821405010.1159/000528755 36630922
     [Google Scholar]
  79. ChenY.L. TongL. ChenY. FuC.H. PengJ.B. JiL.L. miR-153 downregulation alleviates PTSD-like behaviors and reduces cell apoptosis by upregulating the Sigma-1 receptor in the hippocampus of rats exposed to single-prolonged stress.Exp. Neurol.202235211403410.1016/j.expneurol.2022.114034 35259352
     [Google Scholar]
  80. TongL. LiM.D. NieP.Y. ChenY. ChenY.L. JiL.L. miR-132 downregulation alleviates behavioral impairment of rats exposed to single prolonged stress, reduces the level of apoptosis in PFC, and upregulates the expression of MeCP2 and BDNF.Neurobiol. Stress20211410031110.1016/j.ynstr.2021.100311 33718536
     [Google Scholar]
  81. NieP.Y. JiL.L. FuC.H. PengJ.B. WangZ.Y. TongL. miR-132 regulates PTSD-like behaviors in rats following single-prolonged stress through Fragile X-related protein 1.Cell. Mol. Neurobiol.202141232734010.1007/s10571‑020‑00854‑x 32333305
     [Google Scholar]
  82. JiL.L. YeY. NieP.Y. PengJ.B. FuC.H. WangZ.Y. TongL. Dysregulation of miR-142 results in anxiety-like behaviors following single prolonged stress.Behav. Brain Res.201936515716310.1016/j.bbr.2019.03.018 30857769
     [Google Scholar]
  83. ChenY. AnQ. YangS.T. ChenY.L. TongL. JiL.L. MicroRNA-124 attenuates PTSD-like behaviors and reduces the level of inflammatory cytokines by downregulating the expression of TRAF6 in the hippocampus of rats following single-prolonged stress.Exp. Neurol.202235611415410.1016/j.expneurol.2022.114154 35753367
     [Google Scholar]
  84. ChangX. WangJ. JiangH. ShiL. XieJ. Hyperpolarization-activated cyclic nucleotide-gated channels: An emerging role in neurodegenerative diseases.Front. Mol. Neurosci.20191214110.3389/fnmol.2019.00141 31231190
     [Google Scholar]
  85. NiL. XuY. DongS. KongY. WangH. LuG. WangY. LiQ. LiC. DuZ. SunH. SunL. The potential role of the HCN1 ion channel and BDNF-mTOR signaling pathways and synaptic transmission in the alleviation of PTSD.Transl. Psychiatry202010110110.1038/s41398‑020‑0782‑1 32198387
     [Google Scholar]
  86. ZhangX. ZhaoY. DuY. SunH. ZhangW. WangA. LiQ. LiC. WangY. DuZ. SunH. SunL. Effect of ketamine on mood dysfunction and spatial cognition deficits in PTSD mouse models via HCN1–BDNF signaling.J. Affect. Disord.202128624825810.1016/j.jad.2021.02.058 33752039
     [Google Scholar]
  87. WenY. LiB. HanF. WangE. ShiY. Dysfunction of calcium/calmodulin/CaM kinase IIα cascades in the medial prefrontal cortex in post-traumatic stress disorder.Mol. Med. Rep.2012651140114410.3892/mmr.2012.1022 22895536
     [Google Scholar]
  88. ZhengS. HanF. ShiY. WenL. HanD. Single-prolonged-stress-induced changes in autophagy-related proteins Beclin-1, LC3, and p62 in the medial prefrontal cortex of rats with post-traumatic stress disorder.J. Mol. Neurosci.2017621435410.1007/s12031‑017‑0909‑x 28341893
     [Google Scholar]
  89. GeorgeS.A. Rodriguez-SantiagoM. RileyJ. RodriguezE. LiberzonI. The effect of chronic phenytoin administration on single prolonged stress induced extinction retention deficits and glucocorticoid upregulation in the rat medial prefrontal cortex.Psychopharmacology20152321475610.1007/s00213‑014‑3635‑x 24879497
     [Google Scholar]
  90. RossoI.M. CrowleyD.J. SilveriM.M. RauchS.L. JensenJ.E. Hippocampus glutamate and N-Acetyl aspartate markers of excitotoxic neuronal compromise in posttraumatic stress disorder.Neuropsychopharmacology20174281698170510.1038/npp.2017.32 28195577
     [Google Scholar]
  91. Coimbra-CostaD. AlvaN. DuranM. CarbonellT. RamaR. Oxidative stress and apoptosis after acute respiratory hypoxia and reoxygenation in rat brain.Redox Biol.20171221622510.1016/j.redox.2017.02.014 28259102
     [Google Scholar]
  92. AlquraanL. AlzoubiK.H. HammadH. Rababa’hS.Y. MayyasF. Omega-3 fatty acids prevent post-traumatic stress disorder-induced memory impairment.Biomolecules20199310010.3390/biom9030100 30871113
     [Google Scholar]
  93. ArakiM. FuchikamiM. OmuraJ. MiyagiT. NagashimaN. OkamotoY. MorinobuS. The role of glucocorticoid receptors in the induction and prevention of hippocampal abnormalities in an animal model of posttraumatic stress disorder.Psychopharmacology202023772125213710.1007/s00213‑020‑05523‑x 32333135
     [Google Scholar]
  94. LiB. ZhangD. VerkhratskyA. Astrocytes in post-traumatic stress disorder.Neurosci. Bull.202238895396510.1007/s12264‑022‑00845‑6 35349095
     [Google Scholar]
  95. NeyL.J. CrombieK.M. MayoL.M. FelminghamK.L. BowserT. MatthewsA. Translation of animal endocannabinoid models of PTSD mechanisms to humans: Where to next?Neurosci. Biobehav. Rev.2022132769110.1016/j.neubiorev.2021.11.040 34838529
     [Google Scholar]
  96. Gunduz-CinarO. CastilloL.I. XiaM. Van LeerE. BrockwayE.T. PollackG.A. YasminF. BukaloO. LimogesA. Oreizi-EsfahaniS. KondevV. BáldiR. DongA. Harvey-WhiteJ. CinarR. KunosG. LiY. ZweifelL.S. PatelS. HolmesA. A cortico-amygdala neural substrate for endocannabinoid modulation of fear extinction.Neuron20231111930533067.e1010.1016/j.neuron.2023.06.023 37480845
     [Google Scholar]
  97. XieG. GaoX. GuoQ. LiangH. YaoL. LiW. MaB. WuN. HanX. LiJ. Cannabidiol ameliorates PTSD-like symptoms by inhibiting neuroinflammation through its action on CB2 receptors in the brain of male mice.Brain Behav. Immun.202411994596410.1016/j.bbi.2024.05.016 38759736
     [Google Scholar]
  98. XueF. XueS. LiuL. SangH. MaQ. TanQ. WangH. ZhouC. PengZ. Early intervention with electroacupuncture prevents PTSD-like behaviors in rats through enhancing hippocampal endocannabinoid signaling.Prog. Neuropsychopharmacol. Biol. Psychiatry20199317118110.1016/j.pnpbp.2019.03.018 30946940
     [Google Scholar]
  99. JeonM. KimM.S. KongC.H. MinH.S. KangW.C. ParkK. JungS.Y. BaeH.J. ParkS.J. LeeJ.Y. KimJ.W. RyuJ.H. 4-Methoxycinnamic acid ameliorates post-traumatic stress disorder-like behavior in mice by antagonizing the CRF type 1 receptor.Life Sci.202536112327110.1016/j.lfs.2024.123271 39603448
     [Google Scholar]
  100. ZhuJ. WangC. wangY. GuoC. LuP. MouF. ShaoS. Electroacupuncture alleviates anxiety and modulates amygdala CRH/CRHR1 signaling in single prolonged stress mice.Acupunct. Med.202240436937810.1177/09645284211056352 35044840
     [Google Scholar]
  101. TillingerA. ZvozilováA. MachM. HorváthováĽ. DziewiczováL. OsackáJ. Single intranasal administration of Ucn3 affects the development of PTSD symptoms in an animal model.Int. J. Mol. Sci.202425221190810.3390/ijms252211908 39595978
     [Google Scholar]
  102. WangZ. HuX. WangZ. ChenJ. WangL. LiC. DengJ. YueK. WangL. KongY. SunL. Ketamine alleviates PTSD-like effect and improves hippocampal synaptic plasticity via regulation of GSK-3β/GR signaling of rats.J. Psychiatr. Res.202417825926910.1016/j.jpsychires.2024.08.019 39167905
     [Google Scholar]
  103. WangS.C. LinC.C. TzengN.S. TungC.S. LiuY.P. Effects of oxytocin on prosocial behavior and the associated profiles of oxytocinergic and corticotropin-releasing hormone receptors in a rodent model of posttraumatic stress disorder.J. Biomed. Sci.20192612610.1186/s12929‑019‑0514‑0 30898126
     [Google Scholar]
  104. FrijlingJ.L. Preventing PTSD with oxytocin: Effects of oxytocin administration on fear neurocircuitry and PTSD symptom development in recently trauma-exposed individuals.Eur. J. Psychotraumatol.201781130265210.1080/20008198.2017.1302652 28451068
     [Google Scholar]
  105. WangS.C. LinC.C. ChenC.C. TzengN.S. LiuY.P. Effects of oxytocin on fear memory and neuroinflammation in a rodent model of posttraumatic stress disorder.Int. J. Mol. Sci.20181912384810.3390/ijms19123848 30513893
     [Google Scholar]
  106. Le DorzeC. BorrecaA. PignataroA. Ammassari-TeuleM. Gisquet-VerrierP. Emotional remodeling with oxytocin durably rescues trauma-induced behavioral and neuro-morphological changes in rats: A promising treatment for PTSD.Transl. Psychiatry20201012710.1038/s41398‑020‑0714‑0 32066681
     [Google Scholar]
  107. EskandarianS. VafaeiA.A. VaeziG.H. TaherianF. KashefiA. Rashidy-PourA. Effects of systemic administration of oxytocin on contextual fear extinction in a rat model of post-traumatic stress disorder.Basic Clin. Neurosci.201344315322 25337363
     [Google Scholar]
  108. LiM. HanF. ShiY. Expression of locus coeruleus mineralocorticoid receptor and glucocorticoid receptor in rats under single-prolonged stress.Neurol. Sci.201132462563110.1007/s10072‑011‑0597‑1 21584742
     [Google Scholar]
  109. HouY. LiM. JinY. XuF. LiangS. XueC. WangK. ZhaoW. Protective effects of tetramethylpyrazine on dysfunction of the locus coeruleus in rats exposed to single prolonged stress by anti-ER stress mechanism.Psychopharmacology2021238102923293610.1007/s00213‑021‑05908‑6 34231002
     [Google Scholar]
  110. GeorgeS.A. KnoxD. CurtisA.L. AldridgeJ.W. ValentinoR.J. LiberzonI. Altered locus coeruleus–norepinephrine function following single prolonged stress.Eur. J. Neurosci.201337690190910.1111/ejn.12095 23279008
     [Google Scholar]
  111. NwokaforC. SerovaL.I. TanelianA. NahviR.J. SabbanE.L. Variable response of norepinephrine transporter to traumatic stress and relationship to hyperarousal.Front. Behav. Neurosci.20211572509110.3389/fnbeh.2021.725091 34650410
     [Google Scholar]
  112. SalehabadiS. AbrariK. Elahdadi SalmaniM. NasiriM. LashkarboloukiT. Investigating the role of the amygdala orexin receptor 1 in memory acquisition and extinction in a rat model of PTSD.Behav. Brain Res.202038411245510.1016/j.bbr.2019.112455 32044404
     [Google Scholar]
  113. HanD. HanF. ShiY. ZhengS. WenL. Mechanisms of memory impairment induced by Orexin-A via Orexin 1 and Orexin 2 receptors in post-traumatic stress disorder rats.Neuroscience202043212613610.1016/j.neuroscience.2020.02.026 32112915
     [Google Scholar]
  114. KongC.H. MinH.S. JeonM. KangW.C. ParkK. KimM.S. JungS.Y. BaeH.J. ParkS.J. ShinH.K. SeoC.S. RyuJ.H. Cheonwangbosimdan mitigates post-traumatic stress disorder-like behaviors through GluN2B-containing NMDA receptor antagonism in mice.J. Ethnopharmacol.202433011827010.1016/j.jep.2024.118270 38685368
     [Google Scholar]
  115. TraylorM. PersynE. TomppoL. KlassonS. AbediV. BakkerM.K. TorresN. LiL. BellS. Rutten-JacobsL. TozerD.J. GriessenauerC.J. ZhangY. PedersenA. SharmaP. Jimenez-CondeJ. RundekT. GrewalR.P. LindgrenA. MeschiaJ.F. SalomaaV. HavulinnaA. KourkoulisC. CrawfordK. MariniS. MitchellB.D. KittnerS.J. RosandJ. DichgansM. JernC. StrbianD. Fernandez-CadenasI. ZandR. RuigrokY. RostN. LemmensR. RothwellP.M. AndersonC.D. WardlawJ. LewisC.M. MarkusH.S. Helsinki StrokeS.D.P.I-C.A.S.G. Genetic basis of lacunar stroke: A pooled analysis of individual patient data and genome-wide association studies.Lancet Neurol.202120535136110.1016/S1474‑4422(21)00031‑4 33773637
     [Google Scholar]
  116. RiggsL.M. AracavaY. ZanosP. FischellJ. AlbuquerqueE.X. PereiraE.F.R. ThompsonS.M. GouldT.D. (2R,6R)-hydroxynorketamine rapidly potentiates hippocampal glutamatergic transmission through a synapse-specific presynaptic mechanism.Neuropsychopharmacology202045242643610.1038/s41386‑019‑0443‑3 31216563
     [Google Scholar]
  117. LiY. DuY. WangC. LuG. SunH. KongY. WangW. LianB. LiC. WangL. ZhangX. SunL. (2R,6R)-hydroxynorketamine acts through GluA1-induced synaptic plasticity to alleviate PTSD-like effects in rat models.Neurobiol. Stress20222110050310.1016/j.ynstr.2022.100503 36532380
     [Google Scholar]
  118. LeeB. SurB. LeeH. OhS. Korean Red Ginseng prevents posttraumatic stress disorder–triggered depression-like behaviors in rats via activation of the serotonergic system.J. Ginseng Res.202044464465410.1016/j.jgr.2019.09.005 32617045
     [Google Scholar]
  119. LeeB. ChoiG.M. SurB. Silibinin prevents depression-like behaviors in a single prolonged stress rat model: The possible role of serotonin.BMC Complement. Med. Ther.20202017010.1186/s12906‑020‑2868‑y 32143600
     [Google Scholar]
  120. SuA. ChenX. ZhangZ. XuB. WangC. XuZ. Integrated transcriptomic and metabolomic analysis of rat serum to investigate potential target of puerarin in the treatment post-traumatic stress disorder.Ann. Transl. Med.2021924177110.21037/atm‑21‑6009 35071465
     [Google Scholar]
  121. JiangY. WangX. LiX. LiuA. FanQ. YangL. FengB. ZhangK. LuL. QiJ. YangF. SongD. WuY. ZhaoM. LiuS. Tanshinone IIA improves contextual fear‐ and anxiety‐like behaviors in mice via the CREB/BDNF/TrkB signaling pathway.Phytother. Res.202236103932394810.1002/ptr.7540 35801985
     [Google Scholar]
  122. AlzoubiK.H. Al HiloA.S. Al-BalasQ.A. El-SalemK. El-ElimatT. AlaliF.Q. Withania somnifera root powder protects againist post-traumatic stress disorder-induced memory impairment.Mol. Biol. Rep.20194654709471510.1007/s11033‑019‑04915‑3 31218539
     [Google Scholar]
  123. GouL. LiY. LiuS. SangH. LanJ. ChenJ. WangL. LiC. LianB. ZhangX. SunH. SunL. (2R,6R)-hydroxynorketamine improves PTSD-associated behaviors and structural plasticity via modulating BDNF-mTOR signaling in the nucleus accumbens.J. Affect. Disord.202333512914010.1016/j.jad.2023.04.101 37137411
     [Google Scholar]
  124. SerovaL.I. NwokaforC. Van BockstaeleE.J. ReyesB.A.S. LinX. SabbanE.L. Single prolonged stress PTSD model triggers progressive severity of anxiety, altered gene expression in locus coeruleus and hypothalamus and effected sensitivity to NPY.Eur. Neuropsychopharmacol.201929448249210.1016/j.euroneuro.2019.02.010 30878321
     [Google Scholar]
  125. AlzoubiK.H. ShatnawiA. Al-QudahM.A. AlfaqihM.A. Edaravone prevents memory impairment in an animal model of post-traumatic distress.Behav. Pharmacol.,201930(2 and 3-Spec Issue), 201-207.10.1097/FBP.0000000000000479
     [Google Scholar]
  126. AbdullahiP.R. Raeis-AbdollahiE. SameniH. VafaeiA.A. GhanbariA. Rashidy-PourA. Protective effects of morphine in a rat model of post-traumatic stress disorder: Role of hypothalamic-pituitary-adrenal axis and beta- adrenergic system.Behav. Brain Res.202039511286710.1016/j.bbr.2020.112867 32827567
     [Google Scholar]
  127. LinC.C. ChangH.A. TaiY.M. ChenT.Y. WanF.J. ChangC.C. TungC.S. LiuY.P. Subchronic administration of aripiprazole improves fear extinction retrieval of Pavlovian conditioning paradigm in rats experiencing psychological trauma.Behav. Brain Res.201936218118710.1016/j.bbr.2018.12.051 30610908
     [Google Scholar]
  128. JiangH. ChenL. LiY. GaoX. YangX. ZhaoB. LiY. WangY. YuX. ZhangX. FengS. ChaiY. MengH. RenX. BaoT. Effects of acupuncture on regulating the hippocampal inflammatory response in rats exposed to post-traumatic stress disorder.Neurosci. Lett.202379613705610.1016/j.neulet.2023.137056 36621587
     [Google Scholar]
  129. ZhouC.H. XueF. ShiQ.Q. XueS.S. ZhangT. MaX.X. YuL.S. LiuC. WangH.N. PengZ.W. The impact of electroacupuncture early intervention on the brain lipidome in a mouse model of post-traumatic stress disorder.Front. Mol. Neurosci.20221581247910.3389/fnmol.2022.812479 35221914
     [Google Scholar]
  130. HouY. ChenM. WangC. LiuL. MaoH. QuX. ShenX. YuB. LiuS. Electroacupuncture attenuates anxiety-like behaviors in a rat model of post-traumatic stress disorder: The role of the ventromedial prefrontal cortex.Front. Neurosci.20211569015910.3389/fnins.2021.690159 34248490
     [Google Scholar]
  131. LinC.C. HuangK.L. TungC.S. LiuY.P. Hyperbaric oxygen therapy restored traumatic stress-induced dysregulation of fear memory and related neurochemical abnormalities.Behav. Brain Res.201935986187010.1016/j.bbr.2018.07.014 30056129
     [Google Scholar]
  132. KoyuncuoğluT. SevimH. ÇetrezN. MeralZ. GönençB. Kuntsal DertsizE. AkakınD. YükselM. ÇakırÖ.K. High intensity interval training protects from Post Traumatic Stress Disorder induced cognitive impairment.Behav. Brain Res.202139711292310.1016/j.bbr.2020.112923 32976860
     [Google Scholar]
  133. BadourC.L. FloresJ. HoodC.O. JonesA.C. BrakeC.A. TipswordJ.M. PennC.J. McCannJ.P. Concurrent and proximal associations among PTSD symptoms, prescription opioid use, and co-use of other substances: Results from a daily monitoring study.Psychol. Trauma202315336737610.1037/tra0001303 35901427
     [Google Scholar]
  134. RodríguezM.N. ColganD.D. LeydeS. PikeK. MerrillJ.O. PriceC.J. Trauma exposure across the lifespan among individuals engaged in treatment with medication for opioid use disorder: Differences by gender, PTSD status, and chronic pain.Subst. Abuse Treat. Prev. Policy20241912510.1186/s13011‑024‑00608‑8 38702783
     [Google Scholar]
  135. PeckK.R. BadgerG.J. ColeR. HigginsS.T. Moxley-KellyN. SigmonS.C. Prolonged exposure therapy for PTSD in individuals with opioid use disorder: A randomized pilot study.Addict. Behav.202314310768810.1016/j.addbeh.2023.107688 36989699
     [Google Scholar]
  136. PetrakisI.L. Meshberg-CohenS. NichC. KellyM.M. ClaudioT. JaneJ.S. PisaniE. RalevskiE. Cognitive processing therapy (CPT) versus individual drug counseling (IDC) for PTSD for veterans with opioid use disorder maintained on buprenorphine.Am. J. Addict.202433552553310.1111/ajad.13557 38624259
     [Google Scholar]
  137. Fuchs-LeitnerI. YazdiK. GerstgrasserN.W. TholenM.G. GraffiusS.T. SchorbA. RosenleitnerJ. Risk of PTSD due to the COVID-19 pandemic among patients in opioid substitution treatment.Front. Psychiatry20211272946010.3389/fpsyt.2021.729460 34658964
     [Google Scholar]
  138. TanelianA. NankovaB. MiariM. NahviR.J. SabbanE.L. Resilience or susceptibility to traumatic stress: Potential influence of the microbiome.Neurobiol. Stress20221910046110.1016/j.ynstr.2022.100461 35789769
     [Google Scholar]
  139. TanelianA. NankovaB. HuF. SahawnehJ.D. SabbanE.L. Effect of acetate supplementation on traumatic stress-induced behavioral impairments in male rats.Neurobiol. Stress20232710057210.1016/j.ynstr.2023.100572 37781563
     [Google Scholar]
  140. ChenL. ZhangY. WangZ. ZhangZ. WangJ. ZhuG. YangS. Activation of GPER1 by G1 prevents PTSD ‐like behaviors in mice: Illustrating the mechanisms from BDNF/TrkB to mitochondria and synaptic connection.CNS Neurosci. Ther.20243071485510.1111/cns.14855 38992889
     [Google Scholar]
  141. GaoF. WangJ. YangS. JiM. ZhuG. Fear extinction induced by activation of PKA ameliorates anxiety-like behavior in PTSD mice.Neuropharmacology202322210930610.1016/j.neuropharm.2022.109306 36341808
     [Google Scholar]
  142. ChenD. WangJ. CaoJ. ZhuG. cAMP-PKA signaling pathway and anxiety: Where do we go next?Cell. Signal.202412211131110.1016/j.cellsig.2024.111311 39059755
     [Google Scholar]
  143. SuA. ZhangJ. ZouJ. The anxiolytic-like effects of puerarin on an animal model of PTSD.Biomed. Pharmacother.201911510897810.1016/j.biopha.2019.108978 31102911
     [Google Scholar]
  144. CuiJ.J. HuangZ.Y. XieY.H. WuJ.B. XuG.H. LiC.F. ZhangM.M. YiL.T. Gut microbiota mediated inflammation, neuroendocrine and neurotrophic functions involved in the antidepressant-like effects of diosgenin in chronic restraint stress.J. Affect. Disord.202332124225210.1016/j.jad.2022.10.045 36349650
     [Google Scholar]
  145. MalikH. UsmanM. ArifM. AhmedZ. AliG. RaufK. SewellR.D.E. Diosgenin normalization of disrupted behavioral and central neurochemical activity after single prolonged stress.Front. Pharmacol.202314123208810.3389/fphar.2023.1232088 37663254
     [Google Scholar]
  146. ChenX.D. WeiJ.X. WangH.Y. PengY.Y. TangC. DingY. LiS. LongZ.Y. LuX.M. WangY.T. Effects and mechanisms of salidroside on the behavior of SPS-induced PTSD rats.Neuropharmacology202324010972810.1016/j.neuropharm.2023.109728 37742716
     [Google Scholar]
  147. HuJ. LiH. WangX. ChengH. ZhuG. YangS. Novel mechanisms of Anshen Dingzhi prescription against PTSD: Inhibiting DCC to modulate synaptic function and inflammatory responses.J. Ethnopharmacol.202433311842510.1016/j.jep.2024.118425 38848974
     [Google Scholar]
  148. WangJ. ZhaoP. ChengP. ZhangZ. YangS. WangJ. WangX. ZhuG. Exploring the effect of Anshen Dingzhi prescription on hippocampal mitochondrial signals in single prolonged stress mouse model.J. Ethnopharmacol.202432311771310.1016/j.jep.2024.117713 38181935
     [Google Scholar]
  149. ShenF. SongZ. XieP. LiL. WangB. PengD. ZhuG. Polygonatum sibiricum polysaccharide prevents depression-like behaviors by reducing oxidative stress, inflammation, and cellular and synaptic damage.J. Ethnopharmacol.202127511416410.1016/j.jep.2021.114164 33932516
     [Google Scholar]
  150. ShenF. XieP. LiC. BianZ. WangX. PengD. ZhuG. Polysaccharides from Polygonatum cyrtonema Hua reduce depression-like behavior in mice by inhibiting oxidative stress-Calpain-1-NLRP3 signaling axis.Oxid. Med. Cell. Longev.2022202211710.1155/2022/2566917 35498131
     [Google Scholar]
  151. LiM. LiK. ZhangH. JiangY. Study on the mechanism of TMRK electroacupuncture in repairing synaptic plasticity in amygdala and hippocampus to relieve fear memory in PTSD rats.Technol. Health Care2019271Suppl.42544310.3233/THC‑199038 31045558
     [Google Scholar]
  152. ZhouC. XueF. XueS. SangH. LiuL. WangY. CaiM. ZhangZ.J. TanQ. WangH. PengZ. Electroacupuncture pretreatment ameliorates PTSD-like behaviors in rats by enhancing hippocampal neurogenesis via the Keap1/Nrf2 antioxidant signaling pathway.Front. Cell. Neurosci.20191327510.3389/fncel.2019.00275 31293390
     [Google Scholar]
  153. ChenX. LiuC. DuK. ChenY. YangS. ZhuG. WangJ. Effects and mechanisms of electroacupuncture on fear extinction and sleep phase in single prolonged stress mice.Zhongguo Zhenjiu202444892393010.13703/j.0255‑2930.20240305‑0001 39111792
     [Google Scholar]
  154. SalehpourF. MahmoudiJ. KamariF. Sadigh-EteghadS. RastaS.H. HamblinM.R. Brain photobiomodulation therapy: A narrative review.Mol. Neurobiol.20185586601663610.1007/s12035‑017‑0852‑4 29327206
     [Google Scholar]
  155. ZhaoC. LiD. KongY. LiuH. HuY. NiuH. JensenO. LiX. LiuH. SongY. Transcranial photobiomodulation enhances visual working memory capacity in humans.Sci. Adv.2022848eabq321110.1126/sciadv.abq3211 36459562
     [Google Scholar]
  156. LiY. DongY. YangL. TuckerL. YangB. ZongX. HamblinM.R. ZhangQ. Transcranial photobiomodulation prevents PTSD-like comorbidities in rats experiencing underwater trauma.Transl. Psychiatry202111127010.1038/s41398‑021‑01389‑5 33953158
     [Google Scholar]
  157. LiY. DongY. YangL. TuckerL. ZongX. BrannD. HamblinM.R. VazdarjanovaA. ZhangQ. Photobiomodulation prevents PTSD-like memory impairments in rats.Mol. Psychiatry202126116666667910.1038/s41380‑021‑01088‑z 33859360
     [Google Scholar]
  158. ZhaoH. LiY. LuoT. ChouW. SunT. LiuH. QiuH. ZhuD. ChenD. GuY. Preventing Post-Traumatic Stress Disorder (PTSD) in rats with pulsed 810 nm laser transcranial phototherapy.Transl. Psychiatry202313128110.1038/s41398‑023‑02583‑3 37580354
     [Google Scholar]
  159. JungJ.T.K. MarquesL.S. ZborowskiV.A. SilvaG.L. NogueiraC.W. ZeniG. Resistance training modulates hippocampal neuroinflammation and protects anxiety-depression-like dyad induced by an emotional single prolonged stress model.Mol. Neurobiol.202360126427610.1007/s12035‑022‑03069‑x 36261694
     [Google Scholar]
  160. ChangS.H. ChenH.Y. ShawF.Z. ShyuB.C. Early- and late-phase changes of brain activity and early-phase neuromodulation in the posttraumatic stress disorder rat model.Neurobiol. Stress20232610055410.1016/j.ynstr.2023.100554 37576348
     [Google Scholar]
  161. HanF. JiangJ. DingJ. LiuH. XiaoB. ShiY. Change of Rin1 and Stathmin in the animal model of traumatic stresses.Front. Behav. Neurosci.2017116210.3389/fnbeh.2017.00062 28491025
     [Google Scholar]
  162. SzeszkoP.R. LehrnerA. YehudaR. Glucocorticoids and hippocampal structure and function in PTSD.Harv. Rev. Psychiatry201826314215710.1097/HRP.0000000000000188 29734228
     [Google Scholar]
  163. FischerS. SchumacherT. KnaevelsrudC. EhlertU. SchumacherS. Genes and hormones of the hypothalamic-pituitary-adrenal axis in post-traumatic stress disorder. What is their role in symptom expression and treatment response?J. Neural Transm.202112891279128610.1007/s00702‑021‑02330‑2 33825945
     [Google Scholar]
  164. Ganon-ElazarE. AkiravI. Cannabinoids prevent the development of behavioral and endocrine alterations in a rat model of intense stress.Neuropsychopharmacology201237245646610.1038/npp.2011.204 21918506
     [Google Scholar]
  165. ZambettiP.R. SchuesslerB.P. LecampB.E. ShinA. KimE.J. KimJ.J. Ecological analysis of Pavlovian fear conditioning in rats.Commun. Biol.20225183010.1038/s42003‑022‑03802‑1 35982246
     [Google Scholar]
  166. JonesM.E. LebonvilleC.L. PanicciaJ.E. BalentineM.E. ReissnerK.J. LysleD.T. Hippocampal interleukin-1 mediates stress-enhanced fear learning: A potential role for astrocyte-derived interleukin-1β.Brain Behav. Immun.20186735536310.1016/j.bbi.2017.09.016 28963000
     [Google Scholar]
  167. MatsukawaM. YoshikawaM. KatsuyamaN. AizawaS. SatoT. The anterior piriform cortex and predator odor responses: Modulation by inhibitory circuits.Front. Behav. Neurosci.20221689652510.3389/fnbeh.2022.896525 35571276
     [Google Scholar]
  168. TylerR.E. WeinbergB.Z.S. LovelockD.F. OrnelasL.C. BesheerJ. Exposure to the predator odor TMT induces early and late differential gene expression related to stress and excitatory synaptic function throughout the brain in male rats.Genes Brain Behav.20201981268410.1111/gbb.12684 32666635
     [Google Scholar]
  169. PhilbertJ. BeeskéS. BelzungC. GriebelG. The CRF1 receptor antagonist SSR125543 prevents stress-induced long-lasting sleep disturbances in a mouse model of PTSD: Comparison with paroxetine and d-cycloserine.Behav. Brain Res.2015279414610.1016/j.bbr.2014.11.006 25446760
     [Google Scholar]
  170. ChengC.M. ChenM.H. TsaiS.J. ChangW.H. TsaiC.F. LinW.C. BaiY.M. SuT.P. ChenT.J. LiC.T. Susceptibility to treatment-resistant depression within families.JAMA Psychiatry202481766367210.1001/jamapsychiatry.2024.0378 38568605
     [Google Scholar]
  171. TseilikmanV.E. TseilikmanO.B. PashkovA.A. IvlevaI.S. KarpenkoM.N. ShatilovV.A. ZhukovM.S. FedotovaJ.O. KondashevskayaM.V. DowneyH.F. ManukhinaE.B. Mechanisms of susceptibility and resilience to PTSD: Role of dopamine metabolism and BDNF expression in the hippocampus.Int. J. Mol. Sci.202223231457510.3390/ijms232314575 36498900
     [Google Scholar]
  172. AlexanderK.S. NalloorR. BuntingK.M. VazdarjanovaA. Investigating individual pre-trauma susceptibility to a PTSD-like phenotype in animals.Front. Syst. Neurosci.2020138510.3389/fnsys.2019.00085 31992972
     [Google Scholar]
  173. NahviR.J. TanelianA. NwokaforC. GodinoA. PariseE. EstillM. ShenL. NestlerE.J. SabbanE.L. Transcriptome profiles associated with resilience and susceptibility to single prolonged stress in the locus coeruleus and nucleus accumbens in male sprague-dawley rats.Behav. Brain Res.202343911416210.1016/j.bbr.2022.114162 36257560
     [Google Scholar]
  174. HuangG. IqbalJ. ShenD. XueY. YangM. JiaX. MicroRNA expression profiles of stress susceptibility and resilience in the prelimbic and infralimbic cortex of rats after single prolonged stress.Front. Psychiatry202314124771410.3389/fpsyt.2023.1247714 37692297
     [Google Scholar]
  175. LaudaniS. TorrisiS.A. AlboniS. BastiaanssenT.F.S. BenattiC. RiviV. MoloneyR.D. FuochiV. FurneriP.M. DragoF. SalomoneS. TasceddaF. CryanJ.F. LeggioG.M. Gut microbiota alterations promote traumatic stress susceptibility associated with p-cresol-induced dopaminergic dysfunctions.Brain Behav. Immun.202310738539610.1016/j.bbi.2022.11.004 36400332
     [Google Scholar]
  176. TroyA.S. WillrothE.C. ShallcrossA.J. GiulianiN.R. GrossJ.J. MaussI.B. Psychological resilience: An affect-regulation framework.Annu. Rev. Psychol.202374154757610.1146/annurev‑psych‑020122‑041854 36103999
     [Google Scholar]
  177. LiH.Y. ZhuM.Z. YuanX.R. GuoZ.X. PanY.D. LiY.Q. ZhuX.H. A thalamic-primary auditory cortex circuit mediates resilience to stress.Cell2023186713521368.e1810.1016/j.cell.2023.02.036 37001500
     [Google Scholar]
  178. RakeshG. MoreyR.A. ZannasA.S. MalikZ. MarxC.E. ClausenA.N. KritzerM.D. SzaboS.T. Resilience as a translational endpoint in the treatment of PTSD.Mol. Psychiatry20192491268128310.1038/s41380‑019‑0383‑7 30867558
     [Google Scholar]
  179. WillmoreL. CameronC. YangJ. WittenI.B. FalknerA.L. Behavioural and dopaminergic signatures of resilience.Nature2022611793412413210.1038/s41586‑022‑05328‑2 36261520
     [Google Scholar]
  180. ZhangX.X. TianY. WangZ.T. MaY.H. TanL. YuJ.T. The epidemiology of Alzheimer’s disease modifiable risk factors and prevention.J. Prev. Alzheimers Dis.20218331332110.14283/jpad.2021.15 34101789
     [Google Scholar]
  181. SeoD. ZhangE.T. PiantadosiS.C. MarcusD.J. MotardL.E. KanB.K. GomezA.M. NguyenT.K. XiaL. BruchasM.R. A locus coeruleus to dentate gyrus noradrenergic circuit modulates aversive contextual processing.Neuron20211091321162130.e610.1016/j.neuron.2021.05.006 34081911
     [Google Scholar]
  182. LiuM. XieJ. SunY. TLR4/MyD88/NF-κB-mediated inflammation contributes to cardiac dysfunction in rats of PTSD.Cell. Mol. Neurobiol.20204061029103510.1007/s10571‑020‑00791‑9 31939007
     [Google Scholar]
  183. SunJ. YuX. HuangpuH. YaoF. Ginsenoside Rb3 protects cardiomyocytes against hypoxia/reoxygenation injury via activating the antioxidation signaling pathway of PERK/Nrf2/HMOX1.Biomed. Pharmacother.201910925426110.1016/j.biopha.2018.09.002 30396083
     [Google Scholar]
  184. Le DorzeC. Gisquet-VerrierP. Sensitivity to trauma-associated cues is restricted to vulnerable traumatized rats and reinstated after extinction by yohimbine.Behav. Brain Res.201631312013410.1016/j.bbr.2016.07.006 27392642
     [Google Scholar]
  185. TanelianA. NankovaB. CheriyanA. ArensC. HuF. SabbanE.L. Differences in gut microbiota associated with stress resilience and susceptibility to single prolonged stress in female rodents.Neurobiol. Stress20232410053310.1016/j.ynstr.2023.100533 36970450
     [Google Scholar]
  186. JavidiH. YadollahieM. Post-traumatic stress disorder.Int. J. Occup. Environ. Med.20123129 23022845
     [Google Scholar]
  187. MayouR. BryantB. EhlersA. Prediction of psychological outcomes one year after a motor vehicle accident.Am. J. Psychiatry200115881231123810.1176/appi.ajp.158.8.1231 11481156
     [Google Scholar]
  188. WangZ. ZuschlagZ.D. MyersU.S. HamnerM. Atomoxetine in comorbid ADHD/PTSD: A randomized, placebo controlled, pilot, and feasibility study.Depress. Anxiety202239428629510.1002/da.23248 35312136
     [Google Scholar]
  189. LinC.C. ChenT.Y. ChengP.Y. LiuY.P. Early life social experience affects adulthood fear extinction deficit and associated dopamine profile abnormalities in a rat model of PTSD.Prog. Neuropsychopharmacol. Biol. Psychiatry202010110991410.1016/j.pnpbp.2020.109914 32165120
     [Google Scholar]
  190. MarquesL.S. JungJ.T.K. ZborowskiV.A. PinheiroR.C. NogueiraC.W. ZeniG. Emotional-Single Prolonged Stress: A promising model to illustrate the gut-brain interaction.Physiol. Behav.202326011407010.1016/j.physbeh.2022.114070 36574940
     [Google Scholar]
  191. ChengW. HanF. ShiY. Neonatal isolation modulates glucocorticoid-receptor function and synaptic plasticity of hippocampal and amygdala neurons in a rat model of single prolonged stress.J. Affect. Disord.201924668269410.1016/j.jad.2018.12.084 30611912
     [Google Scholar]
  192. PitcairnS.R. OrtelliO.A. WeinerJ.L. Effects of early social isolation and adolescent single prolonged stress on anxiety‐like behaviors and voluntary ethanol consumption in female long evans rats.Alcohol. Clin. Exp. Res.20244881586159910.1111/acer.15397 39031683
     [Google Scholar]
/content/journals/cn/10.2174/011570159X377560250629183749
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Use of Single Prolonged Stress to Model Post-traumatic Stress Disorder in Rodents: What We Found and Where to Next?
Curr. Neuropharmacol. 24, 193 (2026); https://doi.org/10.2174/011570159X377560250629183749
/content/journals/cn/10.2174/011570159X377560250629183749
/content/journals/cn/10.2174/011570159X377560250629183749
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  • Article Type:     Review Article
Keyword(s): drug development; neural circuits; pathogenesis; PTSD; rodents; signaling pathways; single prolonged stress

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