Discinesia espontânea em ratos: possível participação de mecanismos oxidativos e dopaminérgicos

Abstract

Tardive dyskinesia is a movement disorder that develops as a result of prolonged use of antipsychotics, mainly the typical ones, in approximately 20% to 25% of patients and, as age increases, it afflicts about 50% of patients with over 55 years old on typical antipsychotic treatment. It is known that individuals who do not use antipsychotics may develop involuntary movement disorders spontaneously and these worsen with age as well. Therefore, this study aimed to investigate a possible participation of oxidative and/or dopaminergic mechanisms of spontaneous dyskinesia in rats. To do so, experiments with male Wistar rats at 40 weeks of age and younger animals at 8 weeks of age. Behavioral characteristics of involuntary movement disorders, which are the numbers of vacuous chewing movements, as well as an exploratory and locomotor activity were evaluated. The cortex, striatum and region containing the substantia nigra were used for the analysis of the activity of the enzyme monoaminoxidase (MAO), the immunoreactivity of the tyrosine hydroxylase (TH) and markers related to oxidative stress. It was observed that adult rats (40-42 weeks of age) had an increase of VCM around of 60% than younger rats (8-10 weeks of age), however, there was a percentage of adult rats with different VCM values and then the results were divided in those that presented low and high values of VCM. There was no significant difference in both the locomotor and exploratory activity of the rats in all groups. There was an increase about 13% in the activity of the MAO-B enzyme in the striatum and cortex, as well as a decrease about 30% in the immunoreactivity of the TH in the striatum, considering that all alterations were related to age. Only the alteration of the MAO-B activity in striatum was related to the number of VCMs. Likewise, alterations in the oxidation of the dichlorofluorescein diacetate (DCFH-DA), catalase activity, proteic thiol content and substances reactive to thiobarbituric acid (TBARS) in different brain structures, though all related to age. Only the oxidation of the DCFH-DA and the catalase activity were altered in relation to the number of VCMs. Hence, most of the alterations in the biochemical markers in rat brains were associated to the age of the animals. The presence of spontaneous VCM in adult rats was associated to alterations in the MAO-B activity in the striatum and DCFH-DA oxidation in the cortex and substantia nigra. It can be concluded that, as in animal models with the use of antipsychotics, age may contribute to the maintenance of involuntary movements also in animals that do not use these drugs.