Majonoside-R2 reverses social isolation stress-induced decrease in pentobarbital sleep in mice: possible involvement of neuroactive steroids.

Majonoside-R2 (MR2) is a major ocotillol-type saponin constituent of Vietnamese ginseng. We investigated the effect of MR2 on the social isolation stress-induced decrease in pentobarbital sleep in mice, and elucidated the possible involvement of neurosteroidal sites of the GABA(A) receptor complex in the pharmacological activity of MR2. MR2 (3.1-6.2 mg/kg, i.p. or 5-10 microg, i.c.v.) dose-dependently reversed the decrease in pentobarbital sleep caused by social isolation stress to the level of sleep in the group-housed mice, but it had no effect on pentobarbital sleep in group-housed mice. Allotetrahydrodeoxycorticosterone (5alpha-pregnane-3alpha,21-diol-20-one, allo-THDOC; 12.5 microg, i.c.v.), the positive allosteric modulator of the GABA(A) receptor, and alpha-helical CRF(9-41) (alpha hCRF; 25 microg, i.c.v.), the corticotropin-releasing factor (CRF) antagonist, also reversed the decrease in pentobarbital sleep caused by social isolation stress. The reversing effects of i.c.v. MR2 and i.c.v. allo-THDOC on the decrease in pentobarbital sleep in isolated mice were significantly attenuated by pregnenolone sulfate (10 microg, i.c.v.), the steroidal negative allosteric modulator of the GABA(A) receptor. In contrast, when injected i.c.v., MR2, as well as allo-THDOC and alpha hCRF, significantly reversed the decrease in pentobarbital sleep induced by pregnenolone sulfate (10 microg, i.c.v.) and CRF (10 microg, i.c.v.) in group-housed mice. These results suggest that the reversing effect of MR2 on the social isolation stress-induced decrease in pentobarbital sleep is mediated by the neurosteroid site on the GABA(A) receptor complex in mice.