Scholarlink

<p>Alcohol consumption before trauma is a prevalent but understudied risk factor for posttraumatic stress disorder (PTSD). This study investigated whether acute ethanol exposure prior to trauma modulates PTSD-like symptom development in rats, identified hippocampal mechanisms involved, and tested an early post-trauma intervention. Adult male Sprague-Dawley rats received ethanol (1.6&#xa0;g/kg, 40% v/v, intraperitoneal) or saline 4&#xa0;h or 30&#xa0;min before predator scent stress (PSS) or sham-PSS exposure. Seven days post-exposure, anxiety-like behavior (elevated plus-maze), acoustic startle response, and cue-induced freezing were assessed using validated cut-off behavioral criteria to classify PTSD-like phenotypes. Hippocampal CA1 dendritic morphology was examined in relation to behavioral outcomes. In parallel cohorts, immunofluorescence quantified hippocampal hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1), neuropeptide Y (NPY), NPY-Y1 receptor (NPY-Y1-R), and brain-derived neurotrophic factor (BDNF) 1&#xa0;h post-PSS. A separate ethanol-pretreated group received subanesthetic intranasal ketamine (0.6&#xa0;mg/kg) via amylolipid nanovesicles (ketamine-ALN) 1&#xa0;h after PSS. Rats administered ethanol 4&#xa0;h—but not 30&#xa0;min—before PSS showed a higher prevalence of PTSD-like phenotypes at 7 days and significantly greater CA1 dendritic retraction. Combined ethanol and PSS exposure was associated with reduced BDNF and NPY levels, increased HCN1, and loss of NPY-Y1-R immunoreactivity, consistent with a hypoexcitable, plasticity-resistant state in the hippocampus. Rats that received early post-PSS ketamine-ALN showed lower cue-induced freezing, a more resilient behavioral profile, and less dendritic atrophy than unloaded-ALN-treated rats. Pre-trauma timed ethanol exposure was associated with a hippocampal “double-hit” involving HCN1 and NPY-Y1-R circuits, together with greater PTSD-like vulnerability. A single early post-trauma intranasal subanesthetic dose of ketamine was associated with a lower prevalence of PTSD-like phenotype, suggesting a promising preventive strategy for alcohol-exposed trauma survivors.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Acute pretrauma ethanol exacerbates PTSD-like phenotype in rats and is reversed by early intranasal ketamine

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月14日

查看全文
  • Bar Eilat Yogev,
  • Gal Levi,
  • Noa Efroni,
  • Amnon C. Sintov,
  • Doron Todder,
  • Joseph Zohar,
  • Hagit Cohen

摘要

Alcohol consumption before trauma is a prevalent but understudied risk factor for posttraumatic stress disorder (PTSD). This study investigated whether acute ethanol exposure prior to trauma modulates PTSD-like symptom development in rats, identified hippocampal mechanisms involved, and tested an early post-trauma intervention. Adult male Sprague-Dawley rats received ethanol (1.6 g/kg, 40% v/v, intraperitoneal) or saline 4 h or 30 min before predator scent stress (PSS) or sham-PSS exposure. Seven days post-exposure, anxiety-like behavior (elevated plus-maze), acoustic startle response, and cue-induced freezing were assessed using validated cut-off behavioral criteria to classify PTSD-like phenotypes. Hippocampal CA1 dendritic morphology was examined in relation to behavioral outcomes. In parallel cohorts, immunofluorescence quantified hippocampal hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1), neuropeptide Y (NPY), NPY-Y1 receptor (NPY-Y1-R), and brain-derived neurotrophic factor (BDNF) 1 h post-PSS. A separate ethanol-pretreated group received subanesthetic intranasal ketamine (0.6 mg/kg) via amylolipid nanovesicles (ketamine-ALN) 1 h after PSS. Rats administered ethanol 4 h—but not 30 min—before PSS showed a higher prevalence of PTSD-like phenotypes at 7 days and significantly greater CA1 dendritic retraction. Combined ethanol and PSS exposure was associated with reduced BDNF and NPY levels, increased HCN1, and loss of NPY-Y1-R immunoreactivity, consistent with a hypoexcitable, plasticity-resistant state in the hippocampus. Rats that received early post-PSS ketamine-ALN showed lower cue-induced freezing, a more resilient behavioral profile, and less dendritic atrophy than unloaded-ALN-treated rats. Pre-trauma timed ethanol exposure was associated with a hippocampal “double-hit” involving HCN1 and NPY-Y1-R circuits, together with greater PTSD-like vulnerability. A single early post-trauma intranasal subanesthetic dose of ketamine was associated with a lower prevalence of PTSD-like phenotype, suggesting a promising preventive strategy for alcohol-exposed trauma survivors.