Investigação da ação central do carvacrol em modelos de ansiedade, depressão e convulsão em camundongos e possíveis mecanismos farmacológicos envolvidos

Abstract

Carvacrol (5-Isopropyl-2-methylphenol) is a monoterpenic phenol present in the essencial oil of many plants. It is the major component of the essential oil fraction of oregano and thyme. This work presents the behavioral effects of carvacrol in animal models of anxiety, depression, sedation and convulsion, such as, elevated plus maze (EPM), open field, rota rod, barbiturate-induced sleeping time, pentilenetetrazole-induced seizures, forced swimming and tail suspension tests. Carvacrol (CVC) was administered orally, to male mice, at single doses of 12.5; 25 and 50 mg/kg. The results showed that CVC had no effect on the spontaneous motor activity in the rota rod test nor in the number of squares crossed in the open field test. However, CVC decreased the number of groomings in the open field test. In the plus maze test, CVC increased all the observed parameters in the EPM test, suggesting a possible anxiolytic effect. Flumazenil, an antagonist of GABAA/Benzodiazepinic receptors, was able to reverse these effects of CVC. Therefore, CVC did not alter the sleep latency and sleeping time in the barbiturate-induced sleeping time test. CVC also presented an antidepressant activity since that the acute treatment of this substance decreased the immobility time in the forced swimming and tail suspension tests without accompanying changes in ambulation in the open-field test. The anti-immobility effect of CVC (25 mg/kg) was not prevented by pre-treatment of mice with p-chlorophenylalanine (PCPA, an inhibitor of serotonin synthesis), prazosin (an α1-adrenoceptor antagonist) and yohimbine (α2-adrenoceptor antagonist). On the other hand, the pre-treatment of mice with SCH23390 (a dopamine D1 receptor antagonist) or sulpiride (a dopamine D2 receptor antagonist) completely blocked the antidepressant-like effect of CVC (25 mg/kg) in the forced swimming test. In the pentilenetetrazole induced seizures test CVC was not able to protect the animals from seizures nor increase the death time. The data suggest that CVC presents anxiolytic effects, probably related with GABAergic system and antidepressant effects that seems to be dependent on its interaction with the dopaminergic system, but not with the serotonergic and noradrenergic systems.