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The impact of predator stress on electroshock seizure threshold: insights into GABAergic, glutamatergic, and serotonergic pathways in mice

Year: 2026

Type: article

Abstract: Post-traumatic stress disorder (PTSD) disrupts neural pathways, increasing susceptibility to neurological disorders, including epilepsy. Stress-induced alterations in glutamatergic, GABAergic, and serotonergic systems influence seizure susceptibility. This study investigates seizure thresholds within a PTSD-relevant mouse model, evaluating the roles of these neurotransmitters. Male NMRI mice were exposed to predator stress using Wistar rats. Seizure thresholds were assessed via electroshock tests at multiple post-stress intervals. Pharmacological interventions, diazepam, MK-801, and fluoxetine, were administered seven days post-stress. Hippocampal tissues were analyzed for GABA A receptor α 1 subunit, NMDAR1, and 5-HT 1A receptor expression, as well as nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and extracellular signal-regulated kinase (ERK) protein levels, utilizing Western blot techniques. Predator stress significantly decreased seizure thresholds in a time-dependent manner, with the highest effect on day 7 ( P < 0.0001). Treatment with diazepam ( P < 0.05), MK-801 ( P < 0.0001), and fluoxetine ( P < 0.0001) reversed these effects, increasing seizure thresholds. Western blot analysis revealed reduced expression of GABA A α 1 , NMDAR1, and 5-HT 1A receptors ( P < 0.001). Additionally, NF-κB levels were elevated while ERK levels were reduced ( P < 0.001). This study shows that predator stress is associated with increased seizure susceptibility and with downregulation of hippocampal GABAAα1R and 5-HT1AR expression, together with enhanced NF-κB activation and reduced ERK signaling. Pharmacological modulation of GABAergic, glutamatergic, and serotonergic pathways reversed the stress-induced reduction in seizure threshold in this model, suggesting that these systems may contribute to stress-related seizure susceptibility.

Source: Behavioral and Brain Functions

DOI: 10.1186/s12993-026-00321-5