Ethanol Extract of Perillae Herba Enhances Pentobarbital-Induced Sleep and Non-Rapid Eye Movement (NREM) Sleep through GABA(A)-ergic Systems

ABSTRACT

Perillae Herba has been traditionally used for the sedation in the oriental countries. Therefore, this study was conducted to determine whether Perillae Herba ethanol extract (PHEE) enhances pentobarbital-induced sleeping behaviors in animals. In addition, the possible mechanisms are demonstrated. PHEE (12.5, 25 and 50 mg/kg. p.o.) reduced the locomotor activity in mice. PHEE reduced sleep latency and augmented the total sleep time in pentobarbital (42 mg/kg, i.p.)-induced sleep in mice. Furthermore, the number of sleeping mice treated with sub-hypnotic pentobarbital (28 mg/kg, i.p.) increased. PHEE (50 mg/kg. p.o.) decreased the sleep/wake cycles and wakefulness, and increased total sleeping time and NREM sleep in electroencephalogram (EEG) of rats. In addition, PHEE (0.1, 1.0 and 10 µg/ml) increased the intracellular Cl⁻ level through the GABA receptors in the hypothalamus of rats. Moreover, the protein of glutamate decarboxylase (GAD) was overexpressed by PFEE. It was found that PHEE enhanced pentobarbital-induced sleeping behaviors through GABA(A)-ergic transmissions.