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 GABAA receptor α1 subunit, NMDAR1, and 5-HT1A 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 GABAAα1, NMDAR1, and 5-HT1A 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.