Melhora no desempenho cognitivo nas tarefas de reconhecimento de objeto e condicionamento aversivo e diminuição de traços de ansiedade em ratos Wistar uma semana após a aplicação aguda de d-LSD

Abstract

The aging processes lead to cognitive decay, evidenced by the deficit in working memory, attention and problem-solving. These changes are caused by a long list of physiological processes, including lower rates of plasticity, decreased arborization and less dendritic spines. Research shows that the application of classic psychedelics, agonists of serotonin 2A receptors, such as lysergic acid diethylamide (d-LSD), psilocybin, ayahuasca, 5-MeO-DMT can cause changes in brain function that persist long after the acute effects. Also, serotonergic agonists induce gene expression related to synaptic plasticity and promote functional and structural neural plasticity. Thus, this project aims to investigate whether different acute doses of the serotonin agonist d-LSD in animals of different ages, young (2-3 months), adults (8-10 months) and old (12-18 months) can modulate in the long term (7 or 14 days) the cognitive performance of Wistar rats in object recognition (ORT) tasks. We also evaluated whether the serotonin agonist can modulate aversive conditioning tasks (ACT) and the elevated plus-maze (EPM) in adult animals. We found that a single dose of d-LSD increases the preference for the new object in young and adult animals. d-LSD alone did not recover performance in old animals, but when it was combined with environmental enrichment there was a significant increase in novelty preference in old animals. Adult rats also showed higher rates of freezing in the ACT and greater time spent in the open arms of the LCE. Thus, our results show that d-LSD appears to positively modulate memory and learning in cognitive tasks, while at the same time decreases the anxiety levels of these animals. Our results also show that d-LSD has the potential to promote cognitive recovery in old animals.