Intermittent short- and long-term alcohol exposures influence alcohol consumption, anxiety-like behaviors, and seizure onset in genetically epilepsy-prone rats

The genetically epilepsy-prone rats (GEPR-3s) are known for their hereditary susceptibility to seizures and anxiety. This study investigates the impact of short-term (1 week) and long-term (4 weeks) intermittent alcohol exposure through a two-bottle choice paradigm on voluntary alcohol intake, anxiety-like behaviors, and acoustically evoked seizure susceptibility in the GEPR-3s. Anxiety behaviors were assessed 24 h post alcohol exposure using the light-dark box (LDB), open field (OFT), and elevated plus maze (EPM), alongside evaluations of seizure susceptibility. The results indicated that after 1 week of alcohol exposure, female GEPR-3s had higher alcohol intake and preference than males, while males increased their intake and preference after 4 weeks. Furthermore, females GEPR-3s exhibited anxiolytic effects in all anxiety tests after short-term alcohol exposure. In contrast, males displayed mixed responses, exhibiting anxiogenic effects in both LDB and OFT tests, and increased time in open arms but decreased exploration in the EPM test. Further, short-term alcohol exposure delayed seizure onset across both sexes, suggesting potential anticonvulsant effects. After 4 weeks of alcohol exposure, male GEPR-3s exhibited anxiogenic effects in both LDB and OFT tests, and reduced locomotion in the EPM test. In contrast, female GEPR-3ss showed anxiogenic effects in the LDB test, but anxiolytic effects in the OFT test, with decreased locomotion in the EPM test. Additionally, long-term alcohol exposure decreased seizure latency, indicating proconvulsant effects. These findings highlight the complex, bidirectional, and temporal dynamics between alcohol consumption, anxiety, and inherited predisposition to epilepsy.