Activation of Sigma-1 receptor ameliorates anxiety-like behavior and cognitive impairments in a rat model of post-traumatic stress disorder

Ji, Lili; Peng, Junbo; Fu, Chang‐Hai; Cao, Dong Hua; Li, Dan; Tong, Lei; Wang, Zhenyu

doi:10.1016/j.bbr.2016.05.056

Cited by 23 publications

(15 citation statements)

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“…A report suggested that the brain-derived neurotrophic factor (BDNF) signaling pathway could be modulated through the Sig-1R chaperone by chronic treatment with antidepressants (15). Our previous study also found that BDNF-TrkB (Tropomyosin receptor kinase B, TrkB)-ERK (extracellular regulated protein kinases, ERK) signaling pathway was involved in the neuroprotective effect in reduction of anxiety-like behaviors by Sig-1R activation in PTSD rats (18). But whether BDNF affects other pathways is unclear.…”

Section: Introductionmentioning

confidence: 85%

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Sigma-1 receptor activation ameliorates anxiety-like behavior through NR2A-CREB-BDNF signaling pathway in a rat model submitted to single-prolonged stress

Peng

et al. 2017

Molecular Medicine Reports

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Accumulating evidence has demonstrated that the σ-1 receptor (σ‑1R) possesses neuroprotective effects and is a potential novel therapeutic target for certain psychiatric diseases, including post‑traumatic stress disorder (PTSD) accompanied with anxiety disorder. It has been reported that σ‑1R agonist treatment could be modulated by the brain‑derived neurotrophic factor (BDNF) signaling pathway. However, it remains unclear whether BDNF and its upstream regulator are mechanistically involved in the therapeutic effect of σ‑1R in PTSD. To address this question, rats were subjected to a single‑prolonged stress (SPS) paradigm and σ‑1R agonist administration. Open‑field and elevated plus maze tests were implemented to evaluate the effect of σ‑1R activation on the improvement of anxiety‑like behaviors. Furthermore, the expression levels of BDNF, phosphorylated cAMP responsive element‑binding protein (CREB) and glutamate receptor ionotropic N‑methyl D‑aspartate 2A (NMDAR2A) were investigated in the hippocampi of rats. It was revealed that the downregulation of BDNF, phosphorylated CREB and NMDAR2A induced by SPS were reversed by σ‑1R activation. Collectively, the results of the present study suggest that the NMDAR2A/CREB/BDNF signaling pathway is involved in the activation of σ‑1R resulting in therapeutic effects for PTSD.

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Section: Introductionmentioning

confidence: 85%

“…After the SPS procedure, PRE-084 or saline was infused at the volume of 0.1 ml/10 g body weight by intraperitoneal injections daily for 7 consecutive days. The dose of PRE-084 was 0.6 mg/kg based on the previous reports (18).…”

Section: Methodsmentioning

confidence: 99%

Sigma-1 receptor activation ameliorates anxiety-like behavior through NR2A-CREB-BDNF signaling pathway in a rat model submitted to single-prolonged stress

Peng

et al. 2017

Molecular Medicine Reports

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“…Similarly, SPS induces impairments in attention and non-fear memory performance. For example, SPS decreases learning performance in a spatial water maze ( 122 , 147 ). However, the interpretation of these results is confounded by re-exposure to water, which is a reminder of the stressor in SPS-exposed rats but not controls ( 106 ) and so may affect performance in this task.…”

Section: Behavioral Effects Of Spsmentioning

confidence: 99%

“…A large number of reports show that SPS produces or increases anxiety-like behavior in these established behavioral models of anxiety ( 120 , 124 , 130 , 167 – 173 ). Studies using modifications to SPS, such as re-exposure to stressors ( 147 ) or the addition of other stressors to the SPS paradigm ( 129 , 139 , 174 – 179 ), also report increased anxiety-like behavior. On the other hand, other studies fail to find a consistent anxiety-like phenotype produced by SPS ( 180 – 184 ).…”

Section: Behavioral Effects Of Spsmentioning

confidence: 99%

“…In neurons, the MAPK pathway appears to be an important regulator of neuroplasticity ( 319 ). Early investigations into the effects of SPS on the MAPK pathway found that SPS increases the phosphorylation (activation) of MAPK in the mPFC ( 171 , 320 , 321 ) and AMY ( 147 , 322 , 323 ). These studies suggest that MAPK signaling plays a role in coordinating transcriptional responses to SPS via activation of cFos ( 320 ), in regulating neuronal apoptosis ( 323 ), and in the behavioral effects of SPS including hyperalgesia ( 171 ) and increased anxiety-like behavior ( 147 ).…”

Section: Neural and Molecular Mechanisms In Spsmentioning

confidence: 99%

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Single-Prolonged Stress: A Review of Two Decades of Progress in a Rodent Model of Post-traumatic Stress Disorder

et al. 2018

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Post-traumatic stress disorder (PTSD) is a common, costly, and often debilitating psychiatric condition. However, the biological mechanisms underlying this disease are still largely unknown or poorly understood. Considerable evidence indicates that PTSD results from dysfunction in highly-conserved brain systems involved in stress, anxiety, fear, and reward. Pre-clinical models of traumatic stress exposure are critical in defining the neurobiological mechanisms of PTSD, which will ultimately aid in the development of new treatments for PTSD. Single prolonged stress (SPS) is a pre-clinical model that displays behavioral, molecular, and physiological alterations that recapitulate many of the same alterations observed in PTSD, illustrating its validity and giving it utility as a model for investigating post-traumatic adaptations and pre-trauma risk and protective factors. In this manuscript, we review the present state of research using the SPS model, with the goals of (1) describing the utility of the SPS model as a tool for investigating post-trauma adaptations, (2) relating findings using the SPS model to findings in patients with PTSD, and (3) indicating research gaps and strategies to address them in order to improve our understanding of the pathophysiology of PTSD.

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Sigma-1 receptor ligand PD144418 and sigma-2 receptor ligand YUN-252 attenuate the stimulant effects of methamphetamine in mice

Tapia

Lever

et al. 2019

Psychopharmacology

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Activation of Sigma-1 receptor ameliorates anxiety-like behavior and cognitive impairments in a rat model of post-traumatic stress disorder

Cited by 23 publications

References 57 publications

Sigma-1 receptor activation ameliorates anxiety-like behavior through NR2A-CREB-BDNF signaling pathway in a rat model submitted to single-prolonged stress

Sigma-1 receptor activation ameliorates anxiety-like behavior through NR2A-CREB-BDNF signaling pathway in a rat model submitted to single-prolonged stress

Single-Prolonged Stress: A Review of Two Decades of Progress in a Rodent Model of Post-traumatic Stress Disorder

Sigma-1 receptor ligand PD144418 and sigma-2 receptor ligand YUN-252 attenuate the stimulant effects of methamphetamine in mice

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