Anxiolytic-like effects of carvacryl acetate, a derivative of carvacrol, in mice

Abstract

Studies showing anxiolytic-like properties of natural products have grown. This paper evaluated if carvacryl acetate (CA) could be studied as an alternative drug to treat anxiety disorders. Elevated plus maze (EPM) tests , light-dark box (LDB) tests, and marble-burying tests (MBTs) were performed on mice. In the first protocol, the anxiolytic-like activities of CA 25, 50, 75 and 100mg/kg at single doses were compared to those of the vehicle, buspirone 5mg/kg (BUSP) and diazepam 1mg/kg (DZP). In the second protocol, the anxiolytic-like actions of CA were tested for GABAergic and serotonergic systems. The time spent in the open arms (TSOA) and the number of open arms entries (NOAE) were measured in EPM; the time spent in the light box (TSLB) and the number of entries to light box (NELB) were measured in LDB; and the number of marbles buried (NMB) were measured in MBT. CA increased TSOA and NOAE in the EPM, as well as TSLB and NELB in the LDB and the NMB in the MBT. The anxiolytic-like activity of CA 25; 50; 75 and 100mg/kg was not associated with psychomotor retardation in the open field test and in the Rota rod test, contrarily with what happened with DZP. In the second protocol, to suggest the mechanism of action of CA, flumazenil 25mg/kg ip (FLU) and WAY 100,635 10mg/kg ip (WAY-5-HT1A antagonist) were also used. FLU+CA100 reduced TSOA in the EPM when compared to CA100 but WAY+CA100 did not. In LDB, FLU+CA100 reduced the TSLB when compared to CA100 but WAY+CA100 did not. In the MBT, FLU+CA100 inhibited the effect of CA100 on the NMB but WAY+CA100 did not. In conclusion, CA seems to have an anxiolytic-like effect, probably due to GABAergic agonist action, without psychomotor side effects.

Keywords: BDZ; BUSP; CA; Carvacryl acetate; DZP; EL; EPM; FLU; GABA; LDB; Light–dark test; MBT; Marble burying test; Mouse; NELB; NF; NMB; NOAE; NSC; OFT; Plus maze test; SSRI; TSLB; TSOA; TSRB; WAY; WAY 100635; benzodiazepinic; buspirone; carvacryl acetate; diazepam; elevated plus-maze test; epoxy-limonene; flumazenil; gamma-aminobutyric acid; light–dark box test; marble-burying test; number of entries to the light box; number of falls; number of marbles buried; number of open arms entries; number of squares crossed; open-field test; selective serotonin reuptake reuptake inhibitor; time spent in light box; time spent in the open arms; time spent on the rotating bar.