Biomolecules & Therapeutics 2008; 16(3): 261-269  
Anxiolytic-Like Effects of Cyclopeptide Fraction Alkaloids of Zizyphi Spinosi Semen: Possible Involvement of GABAA Receptors
Huishan HANa, Yuan MAb, Jae Soon EUNc, Jin-Tae HONGa, and Ki-Wan OHa*
aCollege of Pharmacy, Chungbuk National University, Cheongju 361-763 Korea.
bResearch Institute of Veterinary Medicine, Chungbuk National University, Cheongju, 361-763 Korea.
cCollege of Pharmacy, Woosuk University, Samrye 565-701 Korea
Received: August 1, 2008; Revised: September 1, 2008; Accepted: September 2, 2008; Published online: September 30, 2008.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
This experiment was performed to investigate the anxiolytic-like effects of cyclopeptide fraction alkaloids of Zizyphi Spinosi Semen (CFAZ), by using the experimental paradigms of anxiety, and compared with those of a known anxiolytic, diazepam. CFAZ (8.0 mg/kg, p.o.) increased the percentage of time spent on the open arms and the number of open arms entries in the elevated plus-maze test, increased the number of head dips in the hole-board test, and increased the percentage of center zone ambulatory time in the open-field box. However, CFAZ has no effect on the locomotor activity, while diazepam (2.0 mg/kg, p.o.) significantly reduced locomotor activity. CFAZ did not influence the grip force in the grip strength meter test, either. From the molecular experiments, CFAZ increased chloride influx in cultured cerebellar granule cells. In addition, GABAA receptors γ-subunit were over-expressed by CFAZ in cultured cerebellar granule cells. It is concluded that CFAZ may have anxiolytic-like effects, and these effects may be mediated by GABAA receptors.
Keywords: Zizyphi Spinosi Semen, Cyclopeptide fraction alkaloids, Anxiolytic-like effects, Elevated plus-maze, Hole-board, Open field, Locomotor, Grip strength, Chloride influx, GABAA subunit

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