SUPPRESSION OF OROFACIAL MOVEMENTS BY ROLIPRAM, A CAMP-PHOSPHODIESTERASE INHIBITOR, IN RATS CHRONICALLY TREATED WITH HALOPERIDOL
SUPPRESSION OF OROFACIAL MOVEMENTS BY ROLIPRAM, A CAMP-PHOSPHODIESTERASE INHIBITOR, IN RATS CHRONICALLY TREATED WITH HALOPERIDOL
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DOI：
10.1016/0014-2999(95)00278-s
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发表时间：
1995-08-25
影响因子：
5
通讯作者：
IYO, M
中科院分区：
文献类型：
--
作者：
SASAKI, H;HASHIMOTO, K;IYO, M
我们研究了咯利普兰（一种选择性环腺苷3 '，5'-单磷酸二酯酶IV型抑制剂）和异丁基甲基黄嘌呤（一种非选择性磷酸二酯酶抑制剂）对氟哌啶醇癸酸酯（25 mg/kg，每4周一次，i.m.）在大鼠中，为了检验我们的假设，即恢复先前由于多巴胺D-2受体超敏感性而降低的纹状体环腺苷3 '，5'-单磷酸水平可能抑制这些运动。在最后一次注射后8周进行测试。与对照组相比，氟哌啶醇治疗显著增加运动障碍和纹状体多巴胺D-2受体密度。咯利普兰（0.1-1.0 mg/kg i. p.）以剂量依赖性方式抑制这些运动，而异丁基甲基黄嘌呤（2 mg/kg i. p.）仅轻微抑制了该综合征，并且高于5 mg/kg的剂量i.p产生了其它强烈的运动。这些结果支持了我们的假设，并表明咯利普兰可能对迟发性运动障碍有治疗作用。
We investigated the effects of rolipram, a selective cyclic adenosine 3',5'-monophosphate phosphodiesterase type IV inhibitor, and isobutylmethylxanthine, a nonselective phosphodiesterase inhibitor, on purposeless spontaneous chewing movements and tongue protrusions produced by 24 weeks treatment with haloperidol decanoate (25 mg/kg every 4 weeks i.m.) in rats, to examine our hypothesis that restoration of striatal cyclic adenosine 3',5'-monophosphate levels previously reduced due to dopamine D-2 receptor supersensitivity, may suppress these movements. Tests were performed 8 weeks after the final injection. Haloperidol treatment significantly increased dyskinetic movements and striatal dopamine D-2 receptor density compared with controls. Rolipram (0.1-1.0 mg/kg i.p.) suppressed these movements in a dose-dependent manner, whereas isobutylmethylxanthine (2 mg/kg i.p.) only slightly suppressed the syndrome and doses higher than 5 mg/kg i.p, produced other intensive movements. These results support our hypothesis and suggest that rolipram may have a therapeutic effect on tardive dyskinesia.