ETHANOL-INDUCED LOCOMOTOR STIMULATION IN C57BL/6 MICE FOLLOWING RO15-4513 ADMINISTRATION
ETHANOL-INDUCED LOCOMOTOR STIMULATION IN C57BL/6 MICE FOLLOWING RO15-4513 ADMINISTRATION
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DOI：
10.1007/bf00445553
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发表时间：
1989-01-01
影响因子：
3.4
通讯作者：
HALE, RL
中科院分区：
文献类型：
--
作者：
BECKER, HC;HALE, RL
本研究的目的是检查两种部分苯二氮卓反向激动剂 RO15-4513 和 FG-7142 单独使用以及与乙醇联合使用对 C57BL/6 小鼠运动活性的影响。当单独给药时，1.5 g/kg 乙醇不会显着影响活性，这证实了先前的报告，表明该小鼠品系对乙醇的兴奋特性相对不敏感。当单独施用时，RO15-4513 治疗也没有显着影响运动活动。然而，RO15-4513 (1.5-6 mg/kg) 和乙醇的共同给药显着增加了运动活性。此外，RO15-4513 (6 mg/kg) 暴露的乙醇刺激作用可通过苯二氮卓受体拮抗剂 RO15-1788 预处理完全逆转。相比之下，FG-7142 (10-20 mg/kg) 在注射盐水和乙醇的小鼠中增加了相同程度的活性。 RO15-1788 预处理也阻断了这种效应。 RO15-4513、FG-7142 和 RO15-1788 均不会显着影响血液乙醇浓度。这表明 RO15-4513 通过其在 C57BL/6 小鼠中拮抗乙醇的抑制特性的能力而揭示了乙醇的兴奋作用。
The purpose of this study was to examine the effects of two partial benzodiazepine inverse agonists, RO15-4513 and FG-7142, alone and in combination with ethanol on locomotor activity in C57BL/6 mice. When administered alone, 1.5 g/kg ethanol did not significantly influence activity, confirming previous reports indicating this mouse strain is relatively insensitive to the excitatory properties of ethanol. RO15-4513 treatment also did not significantly influence locomotor activity when administered alone. However, coadministration of RO15-4513 (1.5-6 mg/kg) and ethanol markedly increased locomotor activity. Moreover, the unmasking of ethanol''s stimulant action by RO15-4513 (6 mg/kg) was completely reversed by pretreatment with the benzodiazepine receptor antagonist RO15-1788. In contrast, FG-7142 (10-20 mg/kg) increased activity to the same extent in both saline and ethanol-injected mice. This effect was blocked by RO15-1788 pretreatment as well. Neither RO15-4513, FG-7142, nor RO15-1788 significantly influenced blood ethanol concentrations. It is suggested that RO15-4513 unmasked the stimulant effects of ethanol by virtue of its ability to antagonize the depressant properties of ethanol in C57BL/6 mice.