ArticlePharmacological reports : PR2021
Development and treatment of cognitive inflexibility in sub-chronic stress-re-stress (SRS) model of PTSD.
Article in Pharmacological reports : PR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- The effect of SSRIs on fear learning: a systematic review and meta-analysis.Psychopharmacology · 2023Pooled it
- Neuroimmune mechanisms in PTSD: inflammatory heterogeneity, circuit dysfunction, and biomarker-based subtypes.Molecular biology reports · 2026Review
- Neuroprotective Role of Morin Hydrate in Stress-Re-stress (SRS) Rat Model of PTSD: Mitigation of Cognitive Dysfunction, Anxiety, and Depression via Regulation of Oxidative Stress and Neuroinflammation.Neurochemical research · 2026Article
- Neuroprotective Effects of C-Phycocyanin in Chronic Unpredictable Mild Stress-Exposed Rats: Regulation of Neuroinflammation and CREB/BDNF Signaling.Neurochemical research · 2026Article
- Regorafenib modulates glucose metabolism, insulin/GLP-1 signaling, and tau pathology in an STZ-induced model of Alzheimer's disease.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Distinct septo-hippocampal cholinergic projections separately mediate stress-induced emotional and cognitive deficits.Science advances · 2024Article
- Alzheimer's disease: from early pathogenesis to novel therapeutic approaches.Metabolic brain disease · 2024Review
- Oral Release Kinetics, Biodistribution, and Excretion of Dopants from Barium-Containing Bioactive Glass in Rats.ACS omega · 2024Article
- Madhuca longifolia-hydro-ethanolic-fraction reverses mitochondrial dysfunction and modulates selective GLUT expression in diabetic mice fed with high fat diet.Molecular biology reports · 2024Article
- Emphasizing the Crosstalk Between Inflammatory and Neural Signaling in Post-traumatic Stress Disorder (PTSD).Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCognitive inflexibility is one of the major clinical symptoms of post-traumatic stress disorder (PTSD). Studies have examined the impact of traumatic events on anxiety. However, there were limited reports on the effect of traumatic episodes on cognitive flexibility. Therefore, animal models developing cognitive inflexibility would provide new insight of pathophysiology and pharmacotherapy of PTSD.
methodsMale Wistar rats were subjected to stress-re-stress (SRS) procedure by restraining them for 2 h followed by foot shock (FS) and halothane exposure on day 2 (D-2). Then, the rats were exposed every week to FS as re-stress cue up to D-32. Donepezil (3 mg/kg; po) and sertraline (10 mg/kg; po) dosing was started from D-8 and continued up to D-32.
resultsSRS exposure caused cognitive inflexibility by producing deficits in intra-dimension (ID) and extra-dimension (ED) set-shifting which was significantly attenuated by donepezil. However, sertraline mitigated only ID shift in SRS-subjected rats. SRS-induced PTSD-like symptoms such as fear response, anxiety-like behaviour and cognitive deficits were attenuated by both donepezil and sertraline. Donepezil did not modulate the SRS-induced hypothalamic-pituitary-adrenal (HPA) axis dysfunction and activation of serotonergic and nor-adrenergic system. Interestingly, exposure of SRS caused a decrease in acetylcholine level and increase in acetylcholine esterase activity in prefrontal cortex (PFC) and hippocampus (HIP) which was only mitigated by donepezil. Donepezil significantly attenuated SRS-induced down-regulation of choline-acetyl transferase and α-7 nicotinic acetylcholine receptor expressions in PFC and HIP.
conclusionCognitive inflexibility is developed in the SRS model along with other PTSD-like symptoms which were attenuated by donepezil.
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