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

Abstract

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 μg, 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 (5α-pregnane-3 α,21-diol-20-one, allo-THDOC; 12.5 μg, i.c.v.), the positive allosteric modulator of the GABA A receptor, and α-helical CRF 9-41 (αhCRF; 25 μg, 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 μg, 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 αhCRF, significantly reversed the decrease in pentobarbital sleep induced by pregnenolone sulfate (10 μg, i.c.v.) and CRF (10 μg, 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.