Environmental factors acting during the neonatal period affected the formation of phenotype of adult animals via epigenetic modifications of the genome, e.g. histone acetylation. We studied the effects of blockage of histone deacetylases with sodium valproate on week 1 of life on the behavioral pattern of adult male 129Sv mice. The results of behavioral tests attest to long-term changes in emotional, but not cognitive pattern of adult animals after sodium valproate administration, which manifested in increased anxiety of animals.

The mechanisms supporting the long-term stable effects of early experience consist of modifications to chromatin, including histone acetylation, leading to changes in the structural relationships between DNA and histones [8,13,15,21]. Increases in levels of histone acetylation in brain and in the transcriptional activity of genes after treatment of animals with histone deacetylase blockers lead to improvements in learning [11,18,22]. This same effect is produced by high levels of maternal care in the first week of life [4], due to the resultant increase in the level of histone H3 acetylation close to the promoter of the glucocorticoid receptor gene (exon 1 7 of the GR promoter) in the hippocampus of adult offspring rats [20]. Our data indicate that the effectiveness of early learning is also determined by the level of maternal behavior. Thus, in 129Sv mice, in contrast to C57BL/6J mice, a low level of effectiveness of early olfactory training with simulation of maternal grooming is combined with low levels of maternal behavior in a test based on transfer of offspring to the nest [1]. Females of strain 129Sv have also been shown to devote less time grooming offspring than female C57BL/6J and NIH Swiss mice [7]. It can be suggested that there is a link between the effectiveness of early training and the level of histone acetylation in the brain. In adult animals, trichostatin A, sodium valproate, and sodium butyrate have been used as blockers of histone deacetylases [5]. The literature lacks reports validating the use of trichostatin A and sodium butyrate in young animals. In addition, trichostatin is dissolved in dimethylsulfoxide (DMSO), which is toxic to developing nervous systems [3]. Sodium valproate does not have these disadvantages. S.c. administration of sodium valproate at a dose of 50 mg/kg on postnatal day 1 is known to be well tolerated by mice and to produce significant increases in histone H3 acetylation in the brain [14]. For these reasons, we have selected sodium valThe processes of histone acetylation in the brain underlie both the mechanisms supporting the long-term stable effects of early experience, transmitted to offspring generations by epigenetic inheritance, and learning. However, the role of acetylation in learning has previously been studied only in adult animals: high levels of learning can be linked with high levels of histone H3 acetylation in the brain. The role of acetylation processes in the mechanisms of early learning has not been addressed. We report here our studies of the effects of blockade of histone deacetylation with sodium valproate, which increases the level of acetylation of histone H3, on the outcome of training to olfactory discrimination in 8-day-old mice of strain 129Sv, which have low levels of learning with simulation of maternal grooming. Four doses of sodium valproate, given from day 3 to day 6 of postnatal development, were found to have gender-dependent actions: there were selective improvements in learning in males but not females, though females showed this se...

The somatodendritic structure of projection neurons was morphometrically examined in the nucleus accumbens of human brain. In contrast to reticular neurons, spiny neurons of the nucleus accumbens and dorsal striatum have different somatodendritic structure. In both parts of the striatum, reticular neurons were NADPH-diaphorase-positive.