Belzung C, Misslin R, Vogel E
Laboratoire de Psychophysiologie, Strasbourg, France.
Pharmacol Biochem Behav. 1988 Aug;30(4):867-70. doi: 10.1016/0091-3057(88)90112-8.
In order to better understand the antagonistic effects of the partial inverse agonist of benzodiazepine receptors, RO 15-4513, against the disinhibitory action of ethanol, we examined the effects of RO 15-4513 at a dose (2.0 mg/kg) that did not alter locomotor activity, given alone or in combination with ethanol, on the behavior of mice confronted with the light/dark choice procedure and the staircase test. At this dose, RO 15-4513 given alone was found to have slight anxiogenic properties and when given in combination with ethanol, to completely reverse the disinhibitory effects of ethanol. Since we previously observed postictal depression after higher doses of RO 15-4513 given alone and antagonistic effects of these same doses on the action of ethanol, it can be suggested that the antagonistic effects of RO 15-4513 against ethanol are due to its anxiogenic or depressive properties depending on doses. However, this hypothesis can only be regarded as being in early stages of development at the present time since these results do not parallel with those of several other studies and the question whether the antagonistic action of RO 15-4513 against ethanol is additive or interactive remains open.
为了更好地理解苯二氮䓬受体部分反向激动剂RO 15 - 4513对乙醇去抑制作用的拮抗效应,我们研究了单独给予或与乙醇联合给予时,RO 15 - 4513在不改变运动活性的剂量(2.0 mg/kg)下,对面临明暗选择程序和阶梯试验的小鼠行为的影响。在该剂量下,单独给予RO 15 - 4513被发现具有轻微的致焦虑特性,与乙醇联合给予时,则可完全逆转乙醇的去抑制作用。由于我们之前观察到单独给予较高剂量的RO 15 - 4513后出现发作后抑郁,且这些相同剂量对乙醇的作用具有拮抗效应,因此可以认为RO 15 - 4513对乙醇的拮抗效应取决于剂量,是由其致焦虑或抑郁特性所致。然而,目前这一假设只能被视为处于早期发展阶段,因为这些结果与其他几项研究的结果不一致,并且RO 15 - 4513对乙醇的拮抗作用是相加性还是相互作用性的问题仍未解决。