Adenosine kinase inhibitors attenuate opiate withdrawal via adenosine receptor activation
Adenosine kinase inhibitors attenuate opiate withdrawal via adenosine receptor activation
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DOI：
10.1016/s0014-2999(98)00724-9
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发表时间：
1998-11-27
影响因子：
5
通讯作者：
Coyle, TS
中科院分区：
文献类型：
--
作者：
Kaplan, GB;Coyle, TS
先前的研究已经证明腺苷在介导阿片效应中的作用。本研究探讨了通过腺苷激酶抑制剂治疗间接激活腺苷受体对小鼠阿片戒断表达的影响。小鼠通过皮下植入吗啡颗粒（75 毫克）接受慢性吗啡治疗 72 小时。然后小鼠接受腺苷激酶抑制剂（5'-氨基-5'-脱氧腺苷（2、5、20、40 mg/kg，腹膜内或腹膜内注射）或碘结核菌素（1、2、5 mg/kg，腹膜内注射））的肠胃外治疗，然后注射纳洛酮，并在 20 分钟内测量阿片戒断症状。与媒介物相比，两种腺苷激酶抑制剂以剂量依赖性方式显着减少以下阿片戒断症状：戒断跳跃、牙齿打颤、前爪震颤和前爪踩踏。此外，5'-氨基-5'-脱氧腺苷可显着减少戒断引起的腹泻和体重减轻。 5'-氨基-5'-脱氧腺苷（40 mg/kg）对阿片戒断症状的影响似乎是通过腺苷受体激活介导的，因为腺苷受体拮抗剂咖啡因（20 mg，腹腔注射）预处理可以逆转这种作用，但选择性磷酸二酯酶抑制剂 Po 20-1724（10 mg/kg，腹腔注射）则不能逆转这种作用。通过腺苷激酶抑制剂治疗激活腺苷受体可减弱阿片戒断，这些药物通常可用于治疗戒断综合征。 (C) 1998 Elsevier Science B.V. 保留所有权利。
Previous studies have demonstrated a role for adenosine in mediating opiate effects. This study examines the effects of indirect activation of adenosine receptors, via treatment with adenosine kinase inhibitors, on the expression of opiate withdrawal in mice. Mice receive chronic morphine treatment via implantation of subcutaneous morphine pellets (75 mg) for 72 h. Mice then receive parenteral treatment with adenosine kinase inhibitors, either 5'-amino-5'-deoxyadenosine (2, 5, 20, 40 mg/kg, intraperitoneal or i.p.) or iodotubericidin (1, 2, 5 mg/kg, i.p.), followed by naloxone injection and opiate withdrawal signs are measured over 20 min. Both adenosine kinase inhibitors significantly reduce the following opiate withdrawal signs in a dose-dependent manner compared to vehicle: withdrawal jumps, teeth chattering, forepaw tremors, and forepaw treads. Additionally, 5'-amino-5'-deoxyadenosine significantly reduces withdrawal-induced diarrhea and weight loss. Effects of 5'-amino-5'-deoxyadenosine (40 mg/kg) on opiate withdrawal signs appear to be mediated via adenosine receptor activation as they are reversed by pretreatment by adenosine receptor antagonist caffeine (20 mg, i.p.) but not by selective phosphodiesterase inhibitor Po 20-1724 (10 mg/kg, i.p.). Adenosine receptor activation via adenosine kinase inhibitor treatment attenuates opiate withdrawal and these agents may be generally useful in the treatment of drug withdrawal syndromes. (C) 1998 Elsevier Science B.V. All rights reserved.