Cyclopeptide alkaloid fraction from Zizyphi Spinosi Semen enhances pentobarbital-induced sleeping behaviors

Abstract

This study aimed to investigate effects of cyclopeptide alkaloid fraction of ZSS (CAFZ) on pentobarbital-induced sleeping behaviors and to determine whether these effects were mediated by γ-aminobutyric acid (GABA) receptors Cl − channel activation, using a Western blot technique and Cl − sensitive fluorescence probe. GABA receptors subunits expression and Cl − influx were investigated in cultured cerebellar granule cells. CAFZ shortened sleeping onset and prolonged sleeping time induced by pentobarbital (42 mg/kg). It also significantly increased the falling asleep rate and duration of sleeping time at a sub-hypnotic dosage of pentobarbital (28 mg/kg). In addition, CAFZ in combination with GABA A receptors agonist, muscimol, synergistically prolonged pentobarbital-induced sleeping time. Both of CAFZ and pentobarbital treatment decreased GABA A receptors α-subunit expression, but did not change β- and γ-subunit expression. However, we found CAFZ and pentobarbital increased Cl − influx, CAFZ showed similar effects with muscimol in potentiating Cl − influx inducing effects of low-dose pentobarbital. In conclusion, it is suggested that the enhancement of Cl − influx by CAFZ may play an important role in the potentiation of pentobarbital-induced sleeping behaviors.