Li R, Chuang D M, Wyatt R J, Kirch D G
Neuropsychiatry Branch, National Institute of Mental Health, Neuroscience Center at St. Elizabeths, Washington, D.C. 20032.
Neurochem Res. 1994 Jun;19(6):673-8. doi: 10.1007/BF00967705.
The effects of chronic haloperidol administration on the accumulation of inositol phosphates were examined in rat brain slices pre-labeled with [3H]myo-inositol and incubated with various dopaminergic drugs. Rats were treated with haloperidol-decanoate or its vehicle (sesame oil) for two, four or six weeks. Dopamine and the selective D1 agonist, SKF38393, induced a significant increase in lithium-dependent accumulation of [3H]inositol monophosphate (IP1) in the frontal cortex, hippocampus and striatum of vehicle-treated animals, while the selective D2 agonist quinpirole did not show any effect on IP1 accumulation. The actions of dopamine and SKF38393 were blocked by the D1 antagonist, SCH23390, but not by the D2 antagonist, spiperone, in all three brain regions. Haloperidol treatment did not affect basal phosphoinositide turnover in the three brain regions. Four or six weeks of haloperidol treatment significantly decreased dopamine-induced IP1 accumulation in the striatum (by 30% and 25%, respectively), but not in the frontal cortex and the hippocampus. Four weeks of treatment with haloperidol significantly decreased IP1 levels in the striatal slices when measured in the presence of quinpirole. However, the accumulation of IP1 measured in the presence of SKF38393 was not significantly altered after haloperidol treatment. The loss of dopamine-sensitive IP accumulation was not observed in the presence of spiperone after haloperidol treatment. The number, but not the affinity, of [3H]sulpiride binding sites in the striatum was significantly increased (by 34-46%) after chronic haloperidol treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
在预先用[3H]肌醇标记并与各种多巴胺能药物一起孵育的大鼠脑片中，研究了长期给予氟哌啶醇对肌醇磷酸积累的影响。大鼠用癸酸氟哌啶醇或其载体（芝麻油）治疗两周、四周或六周。多巴胺和选择性D1激动剂SKF38393可使载体处理动物额叶皮质、海马体和纹状体中锂依赖性[3H]肌醇单磷酸（IP1）的积累显著增加，而选择性D2激动剂喹吡罗对IP1积累无任何影响。在所有三个脑区中，多巴胺和SKF38393的作用均被D1拮抗剂SCH23390阻断，但未被D2拮抗剂螺哌隆阻断。氟哌啶醇治疗不影响三个脑区的基础磷酸肌醇周转率。氟哌啶醇治疗四周或六周可显著降低纹状体中多巴胺诱导的IP1积累（分别降低30%和25%），但额叶皮质和海马体中未出现这种情况。在喹吡罗存在下测量时，氟哌啶醇治疗四周可显著降低纹状体切片中的IP1水平。然而，氟哌啶醇治疗后，在SKF38393存在下测量的IP1积累未发生显著改变。氟哌啶醇治疗后，在螺哌隆存在下未观察到多巴胺敏感性IP积累的丧失。长期给予氟哌啶醇后，纹状体中[3H]舒必利结合位点的数量显著增加（增加34 - 46%），但亲和力未改变。（摘要截短于250字）
