Paternal Aggression in Early-life Impairs the Spatial Memory and Passive Avoidance Learning in Adulthood of Male Rats: The Possible Role of .

INTRODUCTION

Negative early-life experiences (e.g. having an aggressive father) can leave long-lastingimpacts on the behavior. However, it is not clear if they influence learning and memory.

METHODS

In this study, we investigated the influences that the presence of an aggressive father had on the level of passive avoidance learning and spatial memory. We also studied the changes in the dopamine receptor D2 () and peroxisome proliferator-activated receptor gamma coactivator 1-α () gene expression in the hippocampus. Then, we evaluated if a antagonist (sulpiride, 0.125, 0.25, or 0.5 μg/rat) could modulate these changes.

RESULTS

We found that the subjects exposed to early-life stress made by aggressive fathers had impaired passive avoidance learning and spatial memory compared to subjects with normal fathers. Treatment with sulpiride improved passive avoidance learning and spatial memory in rats with aggressive fathers. The rats with aggressive fathers also had higher expression of the gene in their hippocampus than those with normal fathers, while the gene expression was not different among groups. Treatment with sulpiride (0.125, 0.25, or 0.5 μg/rat) reduced the gene expression in those with aggressive fathers to the normal level compared to those with normal fathers.

CONCLUSION

These data suggest that having and living in a shared place with an aggressive father, even without any physical contact, can detrimentally affect passive avoidance learning and spatial memory which is accompanied by the increased expression of the gene. Also, sulpiride as a dopaminergic antagonist could reverse this process.

HIGHLIGHTS

Having and living with an aggressive father reduced learning and memory in offspring.Having and living with an aggressive father during early life increased gene expression.Sulpiride improved learning and memory and also normalized gene expression.A combination of genetic and environmental factors may modulate learning and memory.

PLAIN LANGUAGE SUMMARY

In this study, we looked at how having an aggressive father, can affect behavior in the long term. We wanted to find out if this factor influences learning and memory. To do this, we investigated how the presence of an aggressive father affected passive avoidance learning and spatial memory in subjects. We also examined specific genes in the brain, called and , which are known to be involved in learning and memory. Specifically, we wanted to see if the expression of these genes in the hippocampus (a region of the brain important for memory) was affected by having and presence of an aggressive father. To understand the role of the gene further, we used a drug called sulpiride, which blocks the action of . We administered sulpiride to the subjects with aggressive fathers to see if it could reverse any negative effects on learning and memory. What we found was that subjects that had aggressive fathers had impaired passive avoidance learning and spatial memory compared to those with normal fathers. However, when we treated the subjects with sulpiride, their learning and memory improved. Additionally, we observed that rats with aggressive fathers had higher levels of the gene in their hippocampus, while the gene expression was not different among the groups. The administration of sulpiride reduced the expression of the gene in rats with aggressive fathers, bringing it back to normal levels similar to those with normal fathers. These findings suggest that having and living in the same environment as an aggressive father, even without direct physical contact, can negatively impact passive avoidance learning and spatial memory. This effect seems to be associated with increased expression of the gene. However, using sulpiride as a dopaminergic antagonist can reverse this process and improve learning and memory in these subjects.