The effect of oxytocin and an enriched environment on anxiety-like behaviour and corticosterone levels in a prenatally stressed febrile seizure rat model.

Abstract

Febrile seizures (FS) are a neurological abnormality which occur following a fever that has resulted from a systemic infection and are characterised by convulsions. These convulsions occur due to abnormally increased signalling of interleukin-1 beta, resulting in increased neuronal hyper-excitability. Furthermore, exposure to prenatal stress has been shown to exacerbate seizure duration, elicit anxiety-like behaviour and corticosterone levels. Oxytocin is a neuropeptide with anxiolytic, social bonding, and stress regulation effects. Therefore, the aim of the study was to assess whether oxytocin can attenuate the anxiety-like behaviour and increased corticosterone in rat offspring exposed to prenatal stress and FS. Sprague Dawley rats were mated. On GND14, prenatal stress was induced on pregnant dams for 1hr/7 days. On PND 14, rat pups were injected with lipopolysaccharide (LPS, 200μg/kg, i.p.) followed 2.5h later by an i.p. injection of kainic acid (KA, 1.75mg/kg). Oxytocin (1mg/kg) was induced via different routes (intraperitoneal or intranasal) as well an enriched environment between PND 22-26. The enriched environment included larger cages (1560cm2) with only 4 pups per cage, compared to those groups not receiving enrichment (646cm2), as well as cardboard rolls and plastic toys. On PND 27-33 the light/dark box and elevated plus maze were used to assess anxiety-like behaviour. On PND 34 all rats were euthanized using a sharp guillotine, trunk blood and hypothalamic tissue were collected for neurochemical analysis (ELISA kit). Our findings confirmed that exposure to both prenatal stress and febrile seizures resulted anxiety-like behaviour and significantly higher plasma corticosterone concentrations compared to their counterparts. Environmental enrichment was significantly effective in attenuating the increased basal corticosterone levels and anxiety-like behaviour seen in the prenatally stressed FS rat. Although direct administration of oxytocin showed higher significance in reducing corticosterone plasma levels when compared to the enriched environment. Furthermore, hypothalamic oxytocin levels were not significant in rat exposed to environmental enrichment while oxytocin treatment showed a significant effect when compared to their counterparts. Therefore, oxytocin administration during early postnatal development shows great potential in reversing the effects of prenatal stress and its subsequent exacerbation of FS.