Chronic Treatment with Mood-Stabilizers Attenuates Abnormal Hyperlocomotion of GluA1-Subunit Deficient Mice

Peer reviewe

Removal of GABA(A) Receptor gamma 2 Subunits from Parvalbumin Neurons Causes Wide-Ranging Behavioral Alterations

Peer reviewe

Effects of chronic drug treatments on social activity on a new territory.

<p>Two or three animals on the same treatment were observed for 10(simultaneously-initiated) contacts. The contacts were shorter (<b>A</b>) but more frequent (<b>B</b>) among the control <i>Gria1−/−</i> mice than among the WT mice. Chronic valproate, but not lithium, moderated the activity of the <i>Gria1−/−</i> mice to the level found in the WT mice. Data are means ± SEM (n = 6–15). *<i>p</i><0.05, ***<i>p</i><0.001 for the differences between genotypes after the same treatment; ^#<i>p</i><0.05 for the differences from the control within the same genotype (two-way ANOVA followed by Bonferroni <i>post-hoc</i> test).</p

Effects of chronic treatments with anticonvulsants lamotrigine and topiramate on behavior of <i>Gria1−/−</i> mice.

<p>Cumulative locomotor activities of <i>Gria1−/−</i> and WT mice treated chronically with lamotrigine- or topiramate-supplemented chow for 5-min time intervals (<b>A, C</b>) and for the whole 2-h experiment (<b>B, D</b>). Data are means ± SEM (n = 8–27). In <b>A</b> and <b>C</b>, the earliest significant point from the control activity has been marked by ^#(<i>p</i><0.05). Topiramate treatment reduced the time spent in open arms of elevated-plus maze (<b>E</b>; means ± SEM, n = 9–12) and increased immobility time in forced swimming test (<b>F</b>; means ± SEM, n = 11–12) in <i>Gria1−/−</i> mice. **<i>p</i><0.01, ***<i>p</i><0.001 for the difference between genotypes after the same treatment; ^#<i>p</i><0.05, ^###<i>p</i><0.001 for the difference from the control within the same genotype (two-way ANOVA followed by Bonferroni <i>post-hoc</i> test).</p

Effects of chronic drug treatments on behaviour of <i>Gria1−/−</i> mice in elevated-maze test of anxiety.

<p>Control <i>Gria1−/−</i> spent more time in the open arms than control WT mice. Chronic lithium and valproate did not affect the time spent in (<b>A</b>) or entries to (<b>B</b>) or distances travelled in open arms (<b>C</b>). Data are means ± SEM (n = 7–12). **<i>p</i><0.01 for the difference between genotypes after the same treatment (two-way ANOVA followed by Bonferroni <i>post-hoc</i> test).</p

Characteristics of the treatment groups and drug concentrations.

<p>Treatment groups, ages at the time of locomotor activity tests in novel cages, and body weights at the beginning and end of treatments are showed. Drug concentrations were analysed from serum samples collected after the locomotor activity tests and presented in mM (lithium) or µM (lamotrigine). Data are means ± SEM. *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.001 compared to body weight at the beginning of treatments (paired <i>t</i>-test), ^#<i>p</i><0.05 for the genotype difference (unpaired <i>t</i>-test).</p

Experimental schedule for different cohorts of mice.

<p>LA, locomotor activity test; EPM, elevated plus maze test; FST, forced swimming test; SD, sucrose drinking; RW, running wheel access; OF, open field test; TST, tail suspension test; SI, social interaction test; AMPH, D-amphetamine-induced LA test.</p

Effects of chronic drug treatments in behavioural despair paradigms.

<p><i>Gria1−/−</i> mice were less immobile than the WT mice in both the forced swimming (FST) and tail suspension (TST) tests. Data are means ± SEM (n = 7–13). **<i>p</i><0.01, ***<i>p</i><0.001 for the differences between genotypes after the same treatment; ^#<i>p</i><0.05 for the differences from the control within the same genotype (two-way ANOVA followed by Bonferroni <i>post-hoc</i> test).</p

Effects of chronic lithium and valproate on sucrose preference and running wheel activity <i>Gria1−/−</i> mice.

<p>Preference for sucrose-containing solution over plain water, with and without an access to running wheels (RW) on sucrose-choice days (S1, S2 and S3) in animals treated with lithium (<b>A</b>) and valproate (<b>C</b>). Running wheel activity during the sucrose-choice days (S1, S2, S3) in animals treated with lithium (<b>B</b>) and valproate (<b>D</b>). Data are means ± SEM (n = 6–14). *<i>p</i><0.05, **<i>p</i><0.01 for the differences between genotypes after the same treatment; ^#<i>p</i><0.05, ^###<i>p</i><0.001 for the differences from the control treatment within the same genotype (two-way ANOVA followed by Bonferroni <i>post-hoc</i> test).</p