Maternal deprivation-caused behavioral abnormalities in adult rats relate to a non-methylation-regulated D2 receptor levels in the nucleus accumbens

Abstract

In this study we investigated the effects of maternal deprivation on adult rats' spatial learning and memory, exploratory, and limbic activity and their correlations with the gene expression of dopamine transporter (DAT) and dopamine D1, D2, D3 receptors (DRD1, DRD2, DRD3) in the nucleus accumbens (NAc). We further investigated whether DNA methylation is involved in the regulation of DRD2 gene expression. Results from our behavioral tests demonstrated that maternal deprivation significantly decreased the spatial learning and memory ability, exploratory ability, and limbic activity in adult rats, while results from our molecular analysis revealed that the mRNA levels of DAT, DRD1, DRD2, and DRD3 were significantly downregulated in maternally deprived rats in comparison to control animals. Correlation analysis in the maternally deprived rats suggested that downregulated DAT and DRD2 mRNA levels significantly correlated with the amount of time required to find the platform, but only DRD2 significantly correlated with the time spent in target quadrant in the Morris water-maze test; DAT, DRD1 and DRD2 mRNA levels significantly correlated with the number of vertical activity, but only DRD2 mRNA level significantly correlated with total distance in the open field test. Conversely, DRD3 mRNA level did not display any correlation with behavioral changes. The methylated CpG levels in the promoter region of DRD2 gene and the expression of DNA methyltransferases 1 (Dnmt1) and 3alpha (Dnmt3alpha) were not significantly changed in maternal deprivation group in comparison to the control group. We concluded that downregulation of DAT, DRD1 and DRD2 gene expression in the NAc is in response to the abnormality in exploratory behaviors; downregulation of DAT and DRD2 expression is in response to the abnormality in spatial learning; downregulation of DRD2 is in response to the abnormality in the spatial memory in maternally deprived rats; whereas DRD3 plays no role in these behaviors. DNA methylation might not be the mechanism to regulate the mRNA level.