Behavioral Phenotype in Heterozygous DAT Rats: Transgenerational Transmission of Maternal Impact and the Role of Genetic Asset

Abstract

Dopamine transporter (DAT) is involved in dopamine (DA) reuptake in presynaptic terminals. Deletion of DAT results in a hyperdopaminergic KO-rat phenotype. To conduct our studies in heterozygous DAT rats, several pedigree lines were created, with known derivation of the allele (i.e., maternal or paternal). Our purpose was to elucidate the role of parental origin rather than maternal care, assessing if maternal maltreatments generated sequelae in female offspring. In the first experiment, female rats and their pups were observed during postnatal lactation. Control dams were WT and heterozygous ones were MAT (but K-MAT, with previous experience of early maltreatment by their KO adoptive dams). WT dams were highly attracted to their offspring (predictably, they spent a lot of time licking their pups); in contrast, K-MAT dams showed strangely comparable levels of caring for their pups and exploring the environment. Subsequently, peculiar features of the circadian cycle were found in adolescent rats with different epigenotypes (WT, MUX = offspring of MAT father, MIK = offspring of K-MAT dam). The MIK epigenotype produced locomotor hyperactivity also during resting hours, well above typical values. The MUX epigenotype, on the other hand, was less active and presented a depression-like profile. This study is unique: maltreatment was generated in a spontaneous way from a DAT-KO mother to offspring. We highlight how future studies will address separate contributions by genotype and upbringing. In conclusion, paternal-allele asset generates sequelae diametrically opposed to the inheritance of early maternal trauma.