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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.