Acute and delayed effects of MK801, GK11 and Memantine treatment at the behavioural and histological levels.

<div><p>(<b>A</b>) Analysis of locomotive behaviour 10 min after the drug administration showed that 5 mg/kg GK11-treated rats exhibited the hyperlocomotive behaviour typically observed shortly after treatment with low dose of a high-affinity NMDAR antagonist. The same tendency was observed after 1 mg/kg MK801treatment. To the contrary, the higher doses of MK801 and Memantine (5 and 50 mg/kg, respectively) induce ataxic effects with reduced maximal speed. (<b>B</b>) Representative traces of individual rats’ routes within the arena during the observation time revealed distinct acute exploratory behaviours after the different treatments. </p> <p>(<b>C</b>, <b>D</b>) 24h after the treatment, GK11-treated rats behaved like control animals, whereas all other treated animals displayed ataxia and reduced exploratory behaviour. </p> <p>Quantitations were performed on 12 rats per group. Statistical analyses were performed using the one-way non-parametric ANOVA statistical test followed by Dunn’s post-tests. *: p<0.05; **: p<0.01; ***:p<0.001 compared to controls. </p> <p>(<b>E</b>) Immunohistological examination of the number of HSP70-positive neurons in the cingulate cortex. Representative images of HSP70 immunostaining: GK11 treatment did not induce any expression of HSP70, whereas a strong signal was observed in pyramidal neurons in MK801- and Memantine-treated rats (scale bar = 250 µm). Inset in MK801 1mg/kg image (scale bar 25 µm). Quantifications were performed in 6 rats per condition. Statistical analyses were performed using the one-way ANOVA statistical test followed by Fisher’s LSD post-tests. *: p<0.05; **: p<0.01; ***:p<0.001 compared to controls. $: p<0.05; $ $: p<0.01; $ $ $: p<0.001 compared to GK11-treated rats.</p>