Estudo dos efeitos comportamentais e neuroquímicos do monoterpeno acetato de citronelila em camundongos

Abstract

The citronellyl acetate is a monoterpene present in the essential oil of various plants with citronella. Studies have shown its activity as anti-inflammatory, antimicrobial substance analgesic, antioxidant, and being their biggest use in veterinary as insect repellent. However, surveys show that its activity as an antidepressant and anxiolytic in experimental models, were not performed. The present study investigated the antidepressant activity in mice in the experimental tests the forced swimming and tail suspension test as well as the involvement of the monoaminergic system in these effects. The neurochemical analysis in order to verify the antioxidant activity in mice submitted to the forced swimming test was also performed. Furthermore, it was also verified anxiolytic activity in the plus maze test, the assessment of motor activity in the open field test, the testing of anticonvulsant activity in pentylenetetrazole-induced seizures and hypnotic activity on the sleeping time induced by pentobarbital. Toxicology and damage to organs (brain, liver and kidney) of the animals was also evaluated. Citronellyl acetate reduced the immobility time in the forced swimming test and tail suspension test, at doses of 50 and 100 mg/kg, p.o. The anti-immobility effect of citronellyl acetate (50 and 100 mg / kg) was reversed by pretreatment with PCPA 100 mg/kg i.p. (inhibitor of serotonin synthesis), Prazosin 1 mg / kg, i.p. (α-1 adrenoceptor antagonist), Yohimbine 1 mg / kg, i.p. (α-2 adrenergic receptor antagonist), SCH233390, 15 mg / kg, s.c. (D1 dopamine antagonist) sulpiride 50 mg / kg, i.p. (dopamine D2 antagonist). Citronellyl acetate did not alter spontaneous locomotor activity of animals in the open field test, and showed no anxiolytic activity in animals in the plus maze test. The analysis of the levels of monoamines showed an increase in the levels of monoamines (NA, DA and 5-HT) at a dose of 100 mg/kg of citronellyl acetate and the dose of 50 mg/kg increased levels of NA in striatum of mice. There was a decrease in the levels of metabolites (DOPAC, 5-HIAA and HVA) in the striatum of mice. Toxicity tests have shown that citronellyl acetate showed a security level five (5) according to the OECD 423 protocol and showed no significant histology alterations in the organs of the animals studied. Thus, the study suggests that the anti-immobility effect of citronelila acetate in the forced swim test is related to its action on adrenergic, dopaminergic and serotonergic receptors, which was evidenced by an increase in the levels of monoamines in the brain, suggesting a possible antidepressant effect of this substance. Don’t have altering the locomotor activity of animals and evidence of anxiolytic effects in plus maze test, and not presented significant toxicological effects.