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Authors & Affiliations
Andrea Grígelová, Anna Mikulecká, Hana Kubová
Abstract
Sexual dimorphism of the developing brain raises the question that early seizures could have distinct effects in immature males and females. This study focuses on the short- and long-term effects of repeated neonatal flurothyl-induced seizures on behavioral responses in male and female rats. A total of 33 Wistar albino rats were used: 17 males (8 controls, 9 treated) and 16 females (7 controls, 9 treated). Animals were repeatedly tested at juvenile and adult ages. At postnatal day 6, the pups were separated from mothers for ~10 minutes (treated: 5 min flurothyl exposure until generalized tonic-clonic seizures manifestation and 5 min recovery; control: 10 min separation). The procedure was repeated 5 times per day with a 2-hour session interval for 5 consecutive days. After recovery, all pups were returned to mothers. We evaluated an integrative set of behavioral responses, including cognitive and emotional dimensions. In the open field test, intrasession habituation disruption was found in flurothyl-treated juvenile males and females, more pronounced at adult age. In the elevated plus maze, flurothyl-treated animals showed decreased locomotor activity. Treated female pups spent more time in the open arms. Furthermore, adult females showed more head dipping activity than juveniles, pattern was more pronounced in treated animals. Reference learning and memory retention (Morris Water Maze) were delayed in flurothyl-treated adult females. The results suggest that exposure to flurothyl results in a non-adaptive anxiety profile with respect to experimental conditions, anxiety-related behavior in females, and impairment of cognitive functions in females.