Involvement of diazepam binding inhibitor and its fragment octadecaneuropeptide in social isolation stress-induced decrease in pentobarbital sleep inmice

Diazepam binding inhibitor(DBI) and its fragment, octadecaneuropeptide (ODN ), are putative endogenous ligands for benzodiazepine (BZD) receptors and h ave been shown to act as an inverse BZD receptor agonist in the brain. A pr evious study suggested that the social isolation stress-induced decrease in pentobarbital sleep in mice was partly due to endogenous substances with a n inverse BZD receptor agonist-like property. In this study, we examined th e effects of DBI and ODN on pentobarbital sleep in group-housed and sociall y isolated mice to test the possible involvement of DBI and ODN in a social isolation-induced decrease in pentobarbital sleep. The socially isolated m ice showed significantly shorter durations of pentobarbital (50 mg/kg, intr aperitoneally, i.p.) sleep compared to the group-housed animals. When injec ted intracerebroventricularly (i.c.v.), DBI and ODN (3 and 10 nmol) dose-de pendently shortened the pentobarbital-induced sleeping time in group-housed mice at the same dose range, but these peptides had no effect on the sleep ing time in socially isolated animals. In contrast, flumazenil (16.5-33 nmo l, i.c.v.), a BZD receptor antagonist, reversed the pentobarbital sleeping time in socially isolated mice to the level of group-housed animals without affecting the sleeping time in group-housed animals. The effects of DBI an d ODN in. group-housed mice were significantly blocked by flumazenil (33 nm ol, i.c.v.). Moreover, the effect of flumazenil in socially isolated mice w as significantly attenuated by DBI and ODN (10 nmol, i.c.v.). These results suggest that the changes in the activity of DBI and/or ODN are partly invo lved in the social isolation-induced decrease in the hypnotic action of pen tobarbital in mice.