HIPPOCAMPAL DOPAMINERGIC MODULATION AND NOVELTY EXPOSURE AS MECHANISMS FOR REVERSING MEMORY DEFICITS INDUCED BY MATERNAL DEPRIVATION

Early-life adversities such as maternal deprivation (MD) are associated with long-lasting impairments in brain development and cognition, particularly affecting memory-related circuits and dopaminergic signaling. Exposure to novelty has been proposed as a strategy to promote synaptic plasticity and memory consolidation. This study investigated whether novelty exposure and dopaminergic pharmacological modulation could reverse object recognition (OR) memory deficits induced by MD (Ethics Approval 041/2022/CEUA/UNIPAMPA). Male Wistar rats (144) were divided into 10 groups combining MD or non-deprivation (ND) with novelty and intrahippocampal infusion of saline, SKF (dopaminergic agonist), or SCH (dopaminergic antagonist). MD was performed from postnatal day 1 to 10 by separating dams from litters for 3 h/day. In adulthood, animals underwent stereotaxic surgery for cannula implantation targeting hippocampal CA1 region. After recovery, animals were exposed to OR task, and selected groups to novelty (a new environment for 5 minutes immediately after OR training). During OR training, all groups explored both objects similarly (P>0.05). In the 24h test session, ND, ND+Novelty, ND+SKF, and ND+Novelty+SCH groups showed memory consolidation (P=0.0067; P=0.0010; P=0.0020; P=0.0023), whereas ND+SCH animals did not (P=0.1488). MD and MD+SCH groups exhibited memory impairment (P=0.1754; P=0.0942), while MD+Novelty and MD+SKF showed preserved memory (P=0.0494; P=0.0076). Memory deficits persisted in MD+Novelty+SCH (P=0.2676). The same pattern of results was observed in the 7-day test session. Overall, these findings indicate that MD induces long-term OR memory deficits that can be reversed by novelty exposure or hippocampal dopaminergic stimulation. Notably, the beneficial effects of novelty depended on hippocampal dopaminergic signaling in MD animals.