PAP 9704, a Korean herbal medicine attenuates methamphetamine-induced hyperlocomotion via adenosine A2A receptor stimulation in mice

The effect of PAP 9704, a traditional prescription in Korea consisting of Polygala tenuifolia, Acorus gramineus, and Poria cocos at a ratio of 1:1:1 (dry weight), on methamphetamine (MA)-induced hyperlocomotion was examined in mice. The increased locomotor activity induced by MA (1 mg/kg/d, i.p. x 7) was significantly attenuated by co-administration with PAP 9704 (100 or 200 mg/kg/d, p.o. x 7) in a dose dependent manner. Consistently, it was found that the hyperlocomotor activity occurred in parallel with the expression of striatal fos-related antigen immunoreactivity. The adenosine A(2A) receptor antagonist, 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (0.5 or 1.0 mg/kg, i.p.), significantly reversed the pharmacological action of PAP 9704 in a dose related manner, but the adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (0.5 or 1.0 mg/kg, i.p.) and the A(2B) receptor antagonist alloxazine (1.5 or 3.0 mg/kg, i.p.) did not significantly affect this pharmacological action. Our results suggest that PAP 9704 prevents MA-induced hyperlocomotion, at least in part, via the stimulation of the adenosine A(2A) receptor.