Mecanismos dopaminérgicos envolvidos na modulação da persistência da memória induzida por diferentes estratégias comportamentais

Abstract

Some long-term memories last for hours or days while others can last for months or years. In view of this, scientists investigate strategies that modulate the memory persistence. The activation of brain regions that stimulate the dopamine release to hippocampus is important and mediate other biochemical processes that culminate in a stronger memory trace. In this sense, pharmacological and non-pharmacological strategies that stimulate this neurotransmitter system are proposed in the literature. Two behavioral strategies capable of stimulating the dopamine release to the hippocampus and improving cognitive processes are: (1) exposure to novelty; and, (2) acute physical exercise. Until this moment, it is known that both strategies act on the D1 family dopaminergic receptors, which include the D1 and D5 receptors. However, these receptors are involved in different signaling cascades, and the exact dopaminergic mechanism by which each strategy improves memory is not clear. Therefore, this study aimed to investigate the involvement of dopaminergic receptors D1 and D5 in the modulatory effect of different stimuli (exposure to novelty and one physical exercise session) on memory persistence. This work involved two main studies, each one designed to study one of these stimuli individually. All experiments were performed using laboratory animals (adult male Wistar rats) and behavior tasks standardized for this model. The memory was evaluated by the object recognition test, with memory evaluation on 24 hours, 7, and 14 days after learning, being possible to verify its consolidation and persistence over the days. Our findings indicate that exposure to a novel environment or one physical exercise session immediately after learning promotes memory persistence through a mechanism that depends on the activation of the hippocampal D1 dopamine receptors. More specifically, we demonstrated that memory persistence promoted by both studied stimuli depends on the activation of the PKA pathway, the second messenger of D1 receptors, but not PKC, the second messenger of D2 receptors.