Resstel, L. B. M. | Search bioRxiv

bioRxiv2020

Fluoxetine treatment prevents cardiovascular changes in baroreflex and chemoreflex in rats subjected to chronic stress

Stress may influence the autonomic regulation, pathogenesis of cardiovascular disease and play an important role in animal behavior as depression. Depression is evidenced as a significant risk factor for cardiovascular changes. This is of great importance as some studies show an association between symptoms of depression and increased risk of cardiovascular disease (CVD) morbidity. Additionality, those alterations can be alleviated by use of antidepressants such as fluoxetine, which is a selective serotonin reuptake inhibitor (SSRIs). The link between depression and cardiovascular changes is known to be mediated in part by autonomic mechanisms that contribute to the regulation of cardiovascular function. However, studies on the effects of SSRIs on cardiovascular autonomic function are inconsistent. Thus, in the present study we investigated, in adult male rats, the effect of chronic and acute treatment with fluoxetine on changes in autonomic mechanisms of baroreflex and chemoreflex induced by the repeated restraint stress (RRS) or chronic variable stress (CVS) on baroreflex and chemoreflex in a protocol of 14 days of stress sessions. The results found demonstrated that exposure to chronic stress (RRS and CVS) promove changes on cardiovascular and ventilatory responses controlled by autonomic reflexes, such as baroreflex and chemoreflex. Additionality, that chronic fluoxetine treatment for 21 days was able to prevent not only anhedonic behavior, but also of autonomic changes cardiovascular induced by chronic stress. Taken together, our results show that pharmacological treatment with fluoxetine may be also helpful to prevent cardiovascular events on account of depressive states, by correcting alterations in autonomic function.

pharmacology and toxicology↗

bioRxiv2017

Elastase-2 knockout mice display anxiogenic- and antidepressant-like phenotype: putative role for BDNF metabolism in prefrontal cortex

Several pieces of evidence indicate that elastase-2 (ELA2; chymotrypsin-like ELA2) is an alternative pathway to the generation of angiotensin II (ANG II). Elastase-2 knockout mice (ELA2KO) exhibit alterations in the arterial blood pressure and heart rate. However, there is no data on the behavioral consequences of ELA2 deletion. In this study we addressed this question, submitting ELA2KO and wild-type (WT) mice to several models sensitive to anxiety- and depression-like, memory, and repetitive behaviors. Our data indicates a higher incidence of barbering behavior in ELA2KO compared to WT, as well as an anxiogenic phenotype, evaluated in the elevated plus maze (EPM). While a decrease in locomotor activity was observed in ELA2KO in EPM, this feature was not the main source of variation in the other parameters analyzed. The marble burying test (MBT) indicated increase in repetitive behavior, observed by a higher number of buried marbles. The actimeter test indicated a decrease in total activity and confirmed the increase in repetitive behavior. The spatial memory was tested by repeated exposure to the actimeter in a 24h interval. Both ELA2KO and WT exhibited decreased activity compared to the first exposure, without any distinction between the genotypes. However, when submitted to the cued fear conditioning, ELA2KO displayed lower levels of freezing behavior in the extinction session when compared to WT, but no difference was observed during the conditioning phase. Increased levels of BDNF were found in the prefrontal cortex but not in the hippocampus of ELA2KO mice compared to WT. Finally, in silico analysis indicates that ELA2 is putatively able to cleave BDNF, and incubation of the purified enzyme with BDNF led to the degradation of the later. Our data suggested an anxiogenic- and antidepressant-like phenotype of ELA2KO, possibly associated with increased levels of BDNF in the prefrontal cortex.

animal behavior and cognition↗