Potenciais efeitos da riparina I sobre prejuízos de memória induzidos pela administração crônica de corticosterona em camundongos

Abstract

Exposure to stress can alter cognitive functions such as learning and memory, and also be associated with the pathophysiology of mood and anxiety disorders. Currently, the anxiolytic and sedative agents for the treatment of such diseases do not cause the improvement of cognitive functions, and some may even worsen, as do the benzodiazepines. In previous studies, riparin I proved be effective in acute animal models predictive of anxiolytic and antidepressant activities, and show low toxicity in vitro. Therefore, considering the potential of natural products as a source of new drugs, the aim of this study is to investigate the effects of riparin I in post-stress memory dysfunctions caused by repeated injections of corticosterone -(CORT). Behavioral tests were used (Open Field, Swimming Forced, Ymaze, Passive Avoidance) and the assessment of BDNF levels as neurochemical test. Groups of animals (n = 10-15, average) received a daily injection of corticosterone (20 mg/kg) or vehicle, sc for 22 days, and additionally administered from the 14th day of treatment until 22th day, vehicle, riparin I (50 mg/kg) or fluvoxamine (50 mg/kg). The behavioral results were recorded in the 14th, 21th and 22th days of treatment, one hour after the last administration of the substances. The results showed that the riparin I did not change locomotor activity of animals, evaluated by the number of crossings in the Open Field test or alter the number of grooming, but increased the number of rearing. In the forced swimming test, the riparin I decreased the immobility time of animals. In the Ymaze, riparin I reversed the cognitive impairment caused by corticosterone, which was evaluated by the number of correct alternations between the arms of the apparatus. In the evaluation of short-term memory in Passive Avoidance, riparin I increased latency for passing from animals to aversive compartment. Riparin I tended to increase BDNF levels in the hippocampus. This study showed that riparin I administration at a dose of 50 mg/kg is able to reverse behavioral and neurochemical changes induced by stress associated with repeated administration of corticosterone. In conclusion, the work provides experimental evidence and opens prospects for further studies which can culminate in a future therapeutic use of riparin I in the treatment of depression and anxiety frames in order to treat or even prevent memory deficits.