PAP 9704, a Korean Herbal Medicine Attenuates Methamphetamine-Induced Hyperlocomotion via Adenosine A2A Receptor Stimulation in Mice

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  • Kwon Yong Soo
    Neurotoxicology program, College of Pharmacy, Kangwon National University, Korea
  • Nabeshima Toshitaka
    Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine
  • Shin Eun-Joo
    Neurotoxicology program, College of Pharmacy, Kangwon National University, Korea
  • Chun Wanjoo
    Department of Pharmacology, College of Medicine, Kangwon National University, Korea
  • Jhoo Jin Hyeong
    Clinical Research Institute, Seoul National University Hospital, Korea
  • Jhoo Wang-Kee
    Neurotoxicology program, College of Pharmacy, Kangwon National University, Korea
  • Wie Myung Bok
    Department of Veterinary Medicine, Kangwon National University, Korea
  • Jang Choon-Gon
    College of Pharmacy, Sungkyunkwan University
  • Chung Heesun
    Division of Narcotic Analysis, The National Institute of Scientific Investigation, Korea
  • Sung Young Eun
    Neurotoxicology program, College of Pharmacy, Kangwon National University, Korea
  • Kim Hyoung-Chun
    Neurotoxicology program, College of Pharmacy, Kangwon National University, Korea

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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.×7) was significantly attenuated by co-administration with PAP 9704 (100 or 200 mg/kg/d, p.o.×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 A2A 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 A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (0.5 or 1.0 mg/kg, i.p.) and the A2B 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 A2A receptor.

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