TETRABENAZINE-INDUCED DEPLETION OF BRAIN MONOAMINES - MECHANISM BY WHICH DESMETHYLIMIPRAMINE PROTECTS CORTICAL NOREPINEPHRINE
TETRABENAZINE-INDUCED DEPLETION OF BRAIN MONOAMINES - MECHANISM BY WHICH DESMETHYLIMIPRAMINE PROTECTS CORTICAL NOREPINEPHRINE
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DOI：
10.1016/0014-2999(84)90563-6
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发表时间：
1984-01-01
影响因子：
5
通讯作者：
TOTARO, JA
中科院分区：
文献类型：
--
作者：
PETTIBONE, DJ;PFLUEGER, AB;TOTARO, JA
用去甲丙咪嗪（DEMETHYMIMPRAMINE，5 mg/kg）[一种抗抑郁药]预处理大鼠，可显著拮抗丁苯那嗪（TBZ）（3 mg/kg）诱导的大鼠皮质去甲肾上腺素（NE）耗竭。特异性α 2-肾上腺素能拮抗剂RX 781094 [咪唑克生]完全阻断了利多卡因的这种保护作用。拮抗TBZ消耗作用的剂量的Escherichia coli导致皮质二羟基苯丙氨酸（DOPA）蓄积快速、最大程度减少，RX 781094也阻断了该作用。与多巴胺一样，α 2-肾上腺素能激动剂可乐定（50 μ g/kg）减少了皮质DOPA的积累，并迅速防止了该脑区域中TBZ诱发的NE损失。RX 781094剂量（0.5-2.0 mg/kg）可加速皮质多巴合成，显著增强阈值剂量TBZ（0.6 mg/kg）的耗竭效应。通过间接刺激α 2-肾上腺素受体降低NE更新，从而明显降低TBZ诱导的皮质NE消耗速率。
Pretreatment of rats with desmethylimipramine (DMI) [an antidepressant] (5 mg/kg) significantly antagonized the tetrabenazine (TBZ)-induced (3 mg/kg) depletion of cortical norepinephrine (NE) in rats. This protective effect of DMI was fully blocked by the specific .alpha.2-adrenergic antagonist, RX 781094 [idazoxan]. The doses of DMI which antagonized the depleting effects of TBZ caused rapid, maximal reductions in cortical dihydroxyphenylalanine (DOPA) accumulation, effects which were also blocked by RX 781094. Like DMI, the .alpha.2-adrenergic agonist, clonidine (50 .mu.g/kg) decreased cortical DOPA accumulation and rapidly prevented the TBZ-evoked loss of NE in this brain region. Doses of RX 781094 (0.5-2.0 mg/kg) which accelerated cortical DOPA synthesis, enhanced significantly the depleting effects of a threshold dose of TBZ (0.6 mg/kg). DMI apparently reduces the rate of TBZ-induced depletion of cortical NE by lowering NE turnover through the indirect stimulation of .alpha.2-adrenoceptors.