Influência benéfica da estimulação tátil em modelos experimentais de depressão: parâmetros neuroquímicos e comportamentais em ratos

Abstract

Depression is a common disease worldwide and although there are several drugs for the treatment of depression, the effectiveness of this pharmacotherapy still presents limitations, possibly due to the difficulty of understanding its pathophysiology. Tactile stimulation (TS) is a manual therapy applied both in early and in adult life. Studies have shown the benefits of TS in rodents in models of psychiatric disorders, including anxiety and addiction. In this study, our objective was to evaluate the influence of TS applied in the neonatal period or adult life in different animal models of depression. The first experiment of this study evaluated the possible positive response of TS on the reversion of depression-like behaviors in adulthood after reserpine administration. Adult female Wistar rats received reserpine once daily for three consecutive days (1mg/kg s.c.). The antidepressant imipramine (10mg/kg i.p.) was used as a positive control. Immediately after the reserpine last administration, the TS protocol started (15min/3xday, 8 days). Afterward, depression behavioral tests were performed and then the animals were euthanized for blood collection, for analysis of corticosterone and adrenocorticotrophic hormone (ACTH) levels in plasma, besides of and prefrontal cortex removal for quantification of BDNF, proBDNF, TrkB, GDNF, GFAP and glucocorticoid receptor (GR) immunoreactivity analyzed by western blotting. We observed that TS reverse the depression-like behaviors induced by reserpine. Besides, our results showed that TS reduced plasma levels of corticosterone and ACTH, and reduced adrenal weight, parameters which were increased by reserpine administration. In the PFC, TS increased BDNF, TrkB, GFAP, and GR immunoreactivity and reduced proBDNF levels. The second experiment of this study aimed to evaluate the effect of neonatal TS (10min/1xday, 8 days) on heterozygous serotonin transporter rats (SERT+/-) and evaluate anxiety and depression-like behaviors in adulthood. After the behavioral analyzes the animals were euthanized, and the basolateral amygdala was removed for the expression of BDNF and its isoforms, glutamatergic and gabaergic components as well as glucocorticoid (GR) and mineralocorticoid (MR) receptors and glucocorticoid responsive-genes. We observed that TS improved the anxiety, depressive-like and social behaviors in SERT+/- rats. In the molecular analyzes, only TS per se showed modifications in in the basolateral amygdala, which decreased BDNF and its isoforms IV and VI, the ratio of GR/MR, the glucocorticoid responsive-genes, as well as the ratio of VGLUT/VGAT, while TS increased the GAD67 levels. As a last section of the thesis, a systematic review was performed to evaluate the impact of TS in rats. A total of 55 studies were identified and we observed that TS in rats showed beneficial influences on behaviors, mainly on emotional behaviors. Also, the effects on the peripheric and central nervous system were observed, in which TS improved important stress markers, such as corticosterone levels and also improved neuroplasticity markers, hypothesizing that TS is an effective tool for the improvement of neurobiological and behavioral response in rats. Considering the results found in this thesis, we can conclude that TS exerts a positive influence on anxiety and depression-like behaviors, confirming the hypothesis that these beneficial effects are associated with HPA axis and neuroplasticity. Besides, the systematic review confirmed these hypotheses of the beneficial effects of TS in rats, especially those observed on neuropsychiatric disorders, such as depression and anxiety.