Efeito fase-dependente da reserpina na promoção de déficit comportamental e alteração neuroquímica na via nigro-estriatal de ratos

Abstract

Reserpine induces a failure in the storage capacity of monoamines in synaptic vesicles, generating a depletion of these substances in the terminal nerve and an increase in oxidative stress. A large body of evidence shows that this drug causes the appearance of motor and non-motor symptoms similar to those seen in Parkinson's disease, with its common application protocol resulting from a light phase, using nocturnal animals as the main experimental model. Some studies, however, realization that in the light phase there is a lower concentration of antioxidants in the animal body, nocturnal animals due to daily fluctuations in the production of enzymes such as catalase and superoxide dismutase, in addition to the neurohormone melatonin, which show peaks during the dark. These oscillations, therefore, can represent a phase-dependent vulnerability to disorders resulting from damage to a DNA structure, lipid peroxidation and protein oxidation. Many parameters of biological rhythmicity are not taken into account when standardizing experimental models, which can distance the animal results from the pathophysiology of some disorders. In view of the interactions of circadian machinery and EO, the objective of this work is to observe whether the pharmacological model of reserpine in rats (Santos et al., 2013), when provided during a dark phase, has the same effect of inducing symptoms DP engines compared to their standard application protocol in the clear phase, as well as neurochemical changes in the nigroestrital pathway. 41 animals were used with an approximate age of 3 months. The animals were prepared for the administration of reserpine in two distinct phases, activity and rest; the effect of the drug on behavior was assessed using the catalepsy test. The animals also have a group assessment of the rest-rest rhythm throughout the experimental procedure. Subsequently, neurochemical parameters related to the quantification of dopaminergic neurons were adopted. The administration of reserpine does not change changes in the activity / rest period of the groups. In catalepsy test we observed that animals treated with the drug had the expected motor loss at the end of the protocol, however the group that has received the treatment with reserpine during the night had the beginning of this motor loss later, in relation to the group that has received the treatment during the day. In the neurochemical evaluation, it was not seen a neuronal loss consolidating in the substancia nigra pars compacta (SNpc) and substancia nigra lateral (SNL), only a ventral tegmental área (VTA) revealed a meaning neuronal loss in the group that includes a reserpine during the night in relation to its control group.