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Paternal Aggression in Early-Life Impairs the Spatial Memory and Passive Avoidance Learning in Adulthood of Male Rats: The Possible Role of Drd2 Publisher



Khalifeh S1 ; Tirbakhsh S1 ; Asadi S2 ; Asadi E2 ; Maleki A2 ; Khodagholi F2 ; Zarrindast MR3, 4 ; Nasehi M1 ; Kheradmand A5
Authors
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Authors Affiliations
  1. 1. Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  2. 2. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  3. 3. Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Pharmacology, School of Pharmacy-International Campus, Iran University of Medical Sciences, Tehran, Iran

Source: Basic and Clinical Neuroscience Published:2023


Abstract

Negative early-life experiences (e.g., having an aggressive father) can leave long-lasting impacts on the behavior. However, it is not clear if they influence learning and memory. 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 (DRD2) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) gene expression in the hippocampus. Then, we evaluated if a DRD2 antagonist (Sulpiride, 0.125, 0.25, or 0.5 μg/rat) could modulate these changes. We found that the subjects exposed to early-life stress made by aggressive fathers had impaired passive avoidance learning and spatial memory than those 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 DRD2 gene in their hippocampus than those with normal fathers, while the PGC-1α gene expression was not different among groups. Treatment with Sulpiride (0.125, 0.25, or 0.5 μg/rat) reduced the DRD2 gene expression in those with aggressive fathers to the normal level in those with normal fathers. These data suggest that 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 DRD2 gene. Also, Sulpiride as a dopaminergic antagonist could reverse this process. © 2023 Iran University of Medical Sciences. All rights reserved.