Shin Eun-Joo, Oh Ki-Wan, Kim Kee-Won, Kwon Yong Soo, Jhoo Jin Hyeong, Jhoo Wang-Kee, Cha Joo-Young, Lim Yong Kwang, Kim In Soon, Kim Hyoung-Chun
Neurotoxicology Program, College of Pharmacy, Korea Institute of Drug Abuse, Kangwon National University, Chunchon 200-701, South Korea.
Life Sci. 2004 Oct 22;75(23):2751-64. doi: 10.1016/j.lfs.2004.04.045.
A recent investigation indicated that Polygala tenuifolia Willdenow extract (PTE) possesses a potential antipsychotic effect. In this study, we examined the effects of PTE on the cocaine-induced changes in locomotor activity, conditioned place preference (CPP), fos-related antigen-immunoreactivity (FRA-IR), and activator protein (AP)-1 DNA binding activity. Cocaine-induced behavioral effects (hyperlocomotion and CPP) occurred in parallel with increases in FRA-IR and AP-1 DNA binding activity in the nucleus accumbens. These responses induced by cocaine were consistently attenuated by concurrent treatment with PTE (25 mg or 50 mg/kg/day, i.p. x 7). The adenosine A2A receptor antagonist, 1,3,7-trimethyl-8-(3-chlorostyrl)xanthine (0.5 or 1.0 mg/kg, i.p.), reversed the PTE-mediated pharmacological action in a dose related manner; neither the adenosine A(1) receptor antagonist, 8-cyclopentyl-1,3-dimethylxanthine (0.5 or 1.0 mg/kg, i.p.) nor the A2B receptor antagonist, alloxazine (1.5 or 3.0 mg/kg, i.p.) significantly affected this pharmacological action. Our results suggest that PTE prevents cocaine-induced behavioral effects, at least in part, via the activation of the adenosine A2A receptor.
最近的一项调查表明，远志提取物（PTE）具有潜在的抗精神病作用。在本研究中，我们研究了PTE对可卡因诱导的运动活动变化、条件性位置偏爱（CPP）、Fos相关抗原免疫反应性（FRA-IR）和激活蛋白（AP）-1 DNA结合活性的影响。可卡因诱导的行为效应（运动亢进和CPP）与伏隔核中FRA-IR和AP-1 DNA结合活性的增加同时出现。同时给予PTE（25毫克或50毫克/千克/天，腹腔注射×7天）可使可卡因诱导的这些反应持续减弱。腺苷A2A受体拮抗剂1,3,7-三甲基-8-（3-氯苯乙烯基）黄嘌呤（0.5或1.0毫克/千克，腹腔注射）以剂量相关的方式逆转了PTE介导的药理作用；腺苷A1受体拮抗剂8-环戊基-1,3-二甲基黄嘌呤（0.5或1.0毫克/千克，腹腔注射）和A2B受体拮抗剂咯嗪（1.5或3.0毫克/千克，腹腔注射）均未显著影响这种药理作用。我们的结果表明，PTE至少部分通过激活腺苷A2A受体来预防可卡因诱导的行为效应。
