Efeitos da administração pós-natal e pré-púbere de agonistas dopaminérgicos sobre o comportamento de camundongos jovens

Abstract

The dopaminergic signaling pathways modulate a wide range of vital functions of the nervous system, among which are motor behavior, memory, attention, learning, affective aspects and reward. Studies have increasingly found the involvement of dopaminergic signaling in the etiology of various neuropsychiatric disorders, as well as its importance for the morphophysiological development of the brain. It has already been shown that dopamine (DA) plays a fundamental role in the formation, maturation and physiological function of the central nervous system, and that there are developmental windows in which an imbalance of this neurotransmitter can lead to changes in the chain, culminating in the manifestation of pathologies with a high degree of dysfunctionality. Pathologies such as schizophrenia, depression, and attention deficit hyperactivity disorder are associated with both changes in dopaminergic signaling and brain morphology. These are pathologies that reflect developmental changes that led to the formation of dysfunctional circuits. But at what exact point of development have these changes begun? Which factor determines the degree of impairment and why are some time windows so critical for susceptibility to permanent damage? In view of these and other questions, the purpose of this study is to analyze the reflexes of increased dopaminergic tonus during the perinatal period (five first days of life), in which there is intense synaptogenesis. The DA overload in the first five days of life, when the neural circuits are still in formation, may cause molecular changes that will be reflected in the behavior of the animal at 30 days. The results showed that although they showed a higher resilience to the behavioral changes, the females that received the D1 agonist SKF 38393 in the postnatal period presented reduction in the hippocampal neural arborization. The acute administration of L-Dopa, quinpirole and SKF 38393 at 30 days of life alters the locomotor and exploratory behavior of females, besides leading to the manifestation of anxious and depressive behaviors in females and males. The administration of L-Dopa in the first five days of life is capable of potentializing some of the behavioral phenotypes caused by the dopaminergic challenge, but not all of them, suggesting that some of the changes induced by the increase in the postnatal tone can be reversed before puberty.