Honokiol Potentiates Pentobarbital-induced Sleeping Behaviors through GABAA Receptor Cl- Channel Activation

This study was undertaken to investigate whether honokiol could enhance the pentobarbital-induced sleeping behaviors through gamma-aminobutyric acid (GABA) receptor Cl- channel activation. Thirty minutes after the oral administration of honokiol, mice were received sodium pentobarbital (42 mg/kg, i.p.). The time elapsed from pentobarbital injection to the loss of the righting reflex was taken as sleeping latency. The time elapsed between the loss and voluntary recovery of the righting reflex was considered as the total sleeping time. Western blot technique and Cl- sensitive fluorescence probe were used to detect the expression of GABA(A) receptor subunits and Cl- influx in the primary cultured cerebellar granule cells. Honokiol (0.1 and 0.2 mglkg) prolonged the sleeping time induced by pentobarbital (42 mg/kg) in a dosage-dependent manner. Honokiol (20 and 50 mu M) increased Cl- influx in primary cultured cerebellar granule cells, and selectively increased the GABA(A) receptor a-subunit expression, but had no effect on the abundance of 0 or gamma-subunits. Chronic treatment with 20 mu M honokiol in primary cultured cerebellar neurons did not affect the abundance of GAD65/67. The results suggested that honokiol could potentiate pentobarbital-induced sleeping through GABAA receptor Cl- channel activation.