Participação do sistema dopaminérgico e endocanabinoide nos déficits de memória induzidos pela privação maternal

Abstract

Early life stressful events, such as maternal deprivation (MD), lead to memory deficits that can persist into adulthood. Molecular and/or morphological alterations in structures important for memory processes, such as the hippocampus, ventral tegmental area, and locus coeruleus, may explain the memory deficits observed in rodent models of MD. Additionally, neurotransmitter systems that modulate the long-term memory consolidation and persistence, such as the dopaminergic and endocannabinoid systems, may be affected by early-life chronic stress. In this thesis, we investigated the effects of MD on learning and memory processes using males and female adult rat and mouse models. Here, we demonstrate that only MD males exhibited recognition memory deficits in adulthood, while females appeared to be unaffected. However, specific pharmacological interventions were able to reverse these deficits in males, and to promote memory persistence regardless of gender or MD exposure. Pharmacological stimulation of the ventral tegmental area immediately after learning was effective in reversing recognition memory deficits in male rats and promoting memory persistence in both sexes, regardless of MD exposure. Additionally, stimulation of the dopaminergic locus coeruleus-hippocampal pathway also showed similar results, reversing memory deficits in male rats and promoting memory persistence in both sexes. However, manipulation of the endocannabinoid system through intraperitoneal infusion of a CB1 agonist was not effective in reversing spatial memory deficits induced by MD in male mice. These results highlight the importance of considering gender differences in stress response and memory regulation, as well as in the evaluation of specific pharmacological interventions potential to mitigate the negative effects of maternal deprivation. This thesis offers valuable insights into the underlying mechanisms of MD on learning and memory effects, as well as potential targets for the development of treatments for stress-related memory issues.