Age-related impact of phenobarbital in suppressing prenatal alcohol exposure-related seizures in developing rats

Prenatal alcohol exposure (PAE) during pregnancy can increase the prevalence of N-methyl-d-aspartate (NMDA)-induced generalized tonic-clonic seizures (GTCSs) in developing rats. However, it is unclear whether phenobarbital (PB) can suppress these PAE-related seizures. To explore this knowledge gap, we investigated the effects of acute PB treatment on NMDA-induced seizures in postpartum rats, prenatally exposed to alcohol on gestational day 18 (GD18), at two developmental stages: day 7 (P7), the equivalent of pre-term neonates, and day 15 (P15), the equivalent of full-term neonates. Timed-pregnant female Sprague–Dawley rats were given a single dose of alcohol or its vehicle on GD18 during the second-trimester equivalent. Male and female postpartum rats were tested for the effectiveness of single-dose treatment with either PB or its vehicle in suppressing NMDA-induced seizures. These seizures include wild running-like behavior (WRLB), flexion seizures (FSs), clonic seizures (CSs), generalized tonic-clonic seizures (GTCSs), and tonic seizures (TSs) in P7 and P15 rats. Analyses revealed that P7 rats were more likely to develop GTCSs after PB administration than P15 rats; this effect was associated with shorter latencies to develop NMDA-induced seizures. Moreover, PAE-related seizure severity is less responsive to PB treatment in P7 rats than in P15 rats. These findings suggest that the PAE-related GTCS model in P7 rats can be used to investigate the mechanisms underlying PB-resistant seizures in developing rats.