Status epilepticus (SE) when occurred during brain development can cause short- and long-term consequences, which are frequently associated with NMDA-mediated glutamatergic excitotoxicity. In the present work, we investigated the putative neuroprotective role of ketamine, an NMDA receptor antagonist, on early life SE-induced acute neuronal death and long-term behavioral abnormalities. Male Wistar rats (16 postnatal days) were induced to SE by LiCl-pilocarpine i.p. administration (3 mEq/kg; 60 mg/kg, respectively). Fifteen or 60min after pilocarpine injection, animals received a ketamine administration (22.5mg/kg i.p.). Neuronal degeneration was assessed 24h after SE induction. Another subset of animals was destined to behavioral tasks in adulthood (75-80 postnatal days). Fluoro-Jade C labeling revealed a marked neuronal death on CA1 hippocampal subfield, habenula, thalamus and amygdala in SE animals. Ketamine post-SE onset treatment prevented neuronal death in all regions assessed. In the elevated plus maze, SE induced an increase in anxiety-like behaviors whereas ketamine administration during seizures was able to prevent this alteration. Ketamine administration in non-SE animals resulted in high anxiety levels. There were no observed differences among groups in the open field task in all parameters analyzed. Our results suggest that ketamine post-SE onset treatment was effective in preventing acute and long-standing alterations caused by SE early in life, which indicates a putative role of glutamatergic system on SE-induced brain damage as well as long-lasting behavioral consequences.
It is well known that rats exhibit elevated levels of activity during the dark phase and reduced levels during the light phase of the photoperiod cycle. However, the information about the influence of the time-of-day on the strategies used to explore the environment is still not understood. Here we tested the hypothesis that time-of-day influences the fine-scale exploratory behaviour of rats, measured in the open field (OF) test, and emotionality of rats, measured in the elevated plus maze (EPM) test. Adult male Wistar rats were subjected to the OF and EPM tests during Morning, Afternoon, or Evening sessions. In the OF, a principal component analysis (PCA) revealed that the Evening group exhibited longer duration of locomotion and rearing, and also higher distance travelled, trip length, inter-stop distance, number of stops and stops per trip compared to other groups. PCA also revealed that the Evening group exhibited shorter time spent at the home base, duration of locomotion along the perimeter and distance travelled along the perimeter compared to other groups. In the EPM test, there was no difference between the groups in any of the parameters evaluated. Our results indicate that the time-of-day may influence the spatio-temporal organization of exploration of rats subjected to unfamiliar environments. These alterations appear to be unrelated to differences in the emotional state of the animals.
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