| Summary: | Background: The link between epilepsy and alcohol consumption is complex, with conflicting reports. To enhance our understanding of this link, we conducted a study to determine how inherited seizure susceptibility affects voluntary alcohol consumption and influences alcohol withdrawal seizures in male and female genetically epilepsy-prone rats (GEPR-3s) compared to Sprague Dawley (SD) rats. Methods: In the first experiment, animals were given access to two bottles simultaneously, one containing water and the other 7.5%, 15%, or 30% (<i>v</i>/<i>v</i>) alcohol three times a week for each dose after acclimation to drinking water. In a second experiment, animals were tested for acoustically evoked alcohol seizures 24 h after the last session of voluntary alcohol consumption. Results: Analysis revealed that GEPR-3s (males and females) had lower alcohol intake and preference than SD rats, particularly at lower alcohol concentrations. However, female GEPR-3s consumed more alcohol and had a higher alcohol preference than males. Furthermore, withdrawal from voluntary alcohol consumption facilitated the onset and duration of seizures in GEPR-3s. Conclusions: Our study suggests that genetic seizure susceptibility in GEPR-3s is negatively associated with alcohol consumption. However, withdrawal from low to moderate amounts of alcohol intake can promote epileptogenesis in the epileptic GEPR-3s.
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