Grupp L A, Perlanski E, Stewart R B
Department of Pharmacology, University of Toronto, Ontario, Canada.
Pharmacol Biochem Behav. 1988 Aug;30(4):823-7. doi: 10.1016/0091-3057(88)90106-2.
Although the serotonin uptake inhibitors have been shown to reduce alcohol intake in both animals and man, the mechanism of this effect is unclear. It is known that enhanced serotonergic activity can stimulate activity in the renin-angiotensin system and that elevated activity in the renin-angiotensin system can reduce voluntary alcohol intake. Therefore, serotonin uptake inhibitors such as fluoxetine might exert their effect on alcohol intake, in part, through the renin-angiotensin system. The present experiment assesses this possibility by examining the effect of the angiotensin converting enzyme inhibitor, enalapril, on the fluoxetine-induced decrease in alcohol intake. Four groups of rats were offered limited access to alcohol for 1 hr each day. When intake stabilized each group was injected with 2.5, 5.0 or 10.0 mg/kg of fluoxetine or the saline vehicle 1 hr prior to the access to alcohol. Fluoxetine produced a dose-dependent decrease in alcohol intake. Following this, all groups received injections of 1 mg/kg of the angiotensin converting enzyme inhibitor, enalapril, 40 min prior to the fluoxetine. Enalapril had no effect on alcohol intake in the saline group, but reversed the suppression in alcohol intake produced by the 2.5 mg/kg and 5.0 mg/kg doses of fluoxetine and partially reversed the effect of the 10.0 mg/kg dose. These findings indicate that the fluoxetine-induced reduction in alcohol intake may, in part, be mediated through the renin-angiotensin system.
尽管血清素摄取抑制剂已被证明能减少动物和人类的酒精摄入量，但其作用机制尚不清楚。已知增强的血清素能活性可刺激肾素-血管紧张素系统的活性，而肾素-血管紧张素系统活性的升高可减少自愿酒精摄入量。因此，像氟西汀这样的血清素摄取抑制剂可能部分通过肾素-血管紧张素系统对酒精摄入量产生影响。本实验通过研究血管紧张素转换酶抑制剂依那普利对氟西汀诱导的酒精摄入量减少的影响来评估这种可能性。将四组大鼠每天限制饮酒1小时。当摄入量稳定后，每组在饮酒前1小时注射2.5、5.0或10.0mg/kg的氟西汀或生理盐水。氟西汀使酒精摄入量呈剂量依赖性减少。在此之后，所有组在注射氟西汀前40分钟注射1mg/kg的血管紧张素转换酶抑制剂依那普利。依那普利对生理盐水组的酒精摄入量没有影响，但逆转了2.5mg/kg和5.0mg/kg剂量氟西汀对酒精摄入量的抑制作用，并部分逆转了10.0mg/kg剂量的作用。这些发现表明，氟西汀诱导的酒精摄入量减少可能部分通过肾素-血管紧张素系统介导。
