EFFECTS OF METHYLENE CHLORIDE-SOLUBLE FRACTION OF JAPANESE ANGELICA ROOT EXTRACT, LIGUSTILIDE AND BUTYLIDENEPHTHALIDE, ON PENTOBARBITAL SLEEP IN GROUP-HOUSED AND SOCIALLY ISOLATED MICE

We previously showed that the extract of Japanese angelica root (JAR-E ) reversed the decrease in pentobarbital (PB) sleep induced by isolati on stress and yohimbine and methoxamine, stimulants of central noradre nergic systems, in mice. Here, we tested the effects of several fracti ons from JAR-E and ligustilide and butylidenephthalide, phthalide comp onents of JAR-E, on PB sleep in isolated mice to elucidate the mechani sm of the action of JAR-E. Methanol-soluble (Met-S) and -insoluble (Me t-IS) fractions were obtained from JAR-E. Methylenechloride-soluble (M C-S) and -insoluble fractions (MC-IS) were prepared from Met-S. MCS (1 1.4-76 mg/kg, p.o.) reversed the isolation stress-induced decrease in PB sleep, but neither Met-IS (0.8-2.4 g/kg, p.o.) nor MC-IS (0.7-2 g/k g, p.o.) had the same effect. The i.p. administration of MC-S exhibite d a similar activity to that observed after the p.o. administration of the same fraction. Ligustilide (5-20 mg/kg, i.p.) and butylidenephtha lide (10-30 mg/kg, i.p.) reversed PB sleep decrease in isolated mice. Both components (20 mg/kg, i.p.) attenuated the suppressive effects of yohimbine (30 nmol, i.c.v.), methoxamine (200 nmol, i.c.v.) and a ben zodiazepine inverse agonist FG7142 (10 mg/kg, i.p.) on PB sleep in gro up-housed mice. These results suggest the contribution of ligustilide and butylidenephthalide to the effect of JAR-E on PB sleep in isolated mice, and implicate central noradrenergic and/or GABA, systems in the effects of these components.