Attenuation of stress-induced excitatory behaviors in mice by valerena-4,7(11)-diene from spikenard

Valerena-4,7(11)-diene (VLD) is a sesquiterpenoid obtained from spikenard (Nardostachys grandiflora DC., syn. Nardostachys chinensis). Volatised spikenard oil had shown sedative effects on mice in the open field test, and VLD was determined to be the principal active constituent [1]. The volatised VLD at the concentration of 300µg/cage reduced mice locomotor activity by 78% and prolonged the continuous sleep time of pentobarbital-treated mice by 2.7 times. In addition, VLD showed anti-depressant effect comparable to imipramine in the forced swimming test. Immobilized time of VLD group was reduced by 33% in comparison with that of control group. Considering the following results, these effects of VLD were seemed to be expressed through both olfactory stimulation and direct CNS stimulation. In the experimentally induced anosmic mice, the effects of VLD were reduced by 52%. The intra venous injection of 0.1mg/ml VLD reduced mice locomotor activity by 53%, and the VLD concentration in the blood was 3.0ng/ml. On the other hand, the mice kept for 60min with volatised VLD had shown much less spontaneous activity, but the VLD blood level was 1.0ng/ml. In addition, VLD had dose dependently reduced the stress-induced behavioural changes in the mice subjected to immobilisation stress. This stress shortened sleeping time in the pentobarbital sleeping test by 47%, and immobilised time in the forced swimming test by 43%. The vaporised VLD completely suppressed these stress-induced excitatory behaviours. Moreover, vaporised VLD reduced this stress-induced rise of serum cortisol level. Our data suggest that valerena-4,7(11)-diene would be useful as an anti-stress agent.