Goeldner F O, Pigatto G, Ribeiro A F, Machado H B, Boerngen-Lacerda R
Department of Pharmacology, Universidade Federal do Parana, 81531-980 Curitiba, PR, Brazil.
Pharmacol Biochem Behav. 2005 Oct;82(2):388-96. doi: 10.1016/j.pbb.2005.09.009. Epub 2005 Oct 10.
The serotonergic system is involved in depression, anxiety and alcoholism. The rewarding properties of ethanol, mainly its anxiolytic and stimulant effects, as well as the development of dependence on ethanol have been related to the serotonergic system. Consequently, the use of selective serotonergic reuptake inhibitors (SSRI) has been proposed in the treatment of alcoholism. In this study we investigated whether acute administration of the SSRIs fluoxetine or paroxetine is able to (i) reverse the behavioral effects induced by chronic ethanol consumption, and conversely, (ii) to determine whether acute ethanol is able to substitute for the chronically induced behavioral effects of fluoxetine or paroxetine. Four groups of male Swiss mice (n=60/group) received daily i.p. saline, ethanol (2 g/kg), fluoxetine (10 mg/kg) or paroxetine (5 mg/kg) for 27 days. On the 28th day, each group was challenged with saline, ethanol, fluoxetine or paroxetine. The 14 groups (SS, SE, SP, SF, EE, ES, EP, EF, PP, PE, PS, FF, FE, and FS) were then tested in open field, activity cage and plus-maze. EP and EF groups were able to reverse the behavioral sensitization to the psychomotor stimulant effects of chronic ethanol administration. In contrast, a sensitized stimulatory effect was observed in chronically fluoxetine- or paroxetine treated mice challenged with ethanol (PE and FE). An anxiolytic effect was observed whether ethanol was substituted for SSRI or, conversely, SSRI was substituted for ethanol. SSRIs facilitated ethanol-induced locomotor sensitization, although SSRIs by themselves are unable to produce the locomotor stimulation similar to that induced by ethanol. Finally, SSRIs are unable to interfere in the ethanol anxiolytic effect.
血清素能系统与抑郁症、焦虑症和酒精中毒有关。乙醇的奖赏特性，主要是其抗焦虑和刺激作用，以及对乙醇的依赖性发展都与血清素能系统有关。因此，有人提出使用选择性血清素再摄取抑制剂（SSRI）来治疗酒精中毒。在本研究中，我们调查了急性给予SSRI氟西汀或帕罗西汀是否能够（i）逆转长期乙醇摄入所诱导的行为效应，反之，（ii）确定急性乙醇是否能够替代氟西汀或帕罗西汀长期诱导的行为效应。四组雄性瑞士小鼠（每组n = 60）连续27天每天腹腔注射生理盐水、乙醇（2 g/kg）、氟西汀（10 mg/kg）或帕罗西汀（5 mg/kg）。在第28天，每组分别用生理盐水、乙醇、氟西汀或帕罗西汀进行激发试验。然后，对这14组（SS、SE、SP、SF、EE、ES、EP、EF、PP、PE、PS、FF、FE和FS）小鼠在旷场、活动笼和十字迷宫中进行测试。EP组和EF组能够逆转对长期乙醇给药所致精神运动性刺激效应的行为敏化。相反，在用乙醇激发的长期接受氟西汀或帕罗西汀治疗的小鼠中观察到敏化刺激效应（PE和FE）。无论用乙醇替代SSRI，还是反之用SSRI替代乙醇，均观察到抗焦虑效应。SSRI促进了乙醇诱导的运动敏化，尽管SSRI本身不能产生与乙醇诱导的类似的运动刺激。最后，SSRI不能干扰乙醇的抗焦虑效应。
