Attenuation of alcohol intake by a serotonin uptake inhibitor: evidence for mediation through the renin-angiotensin system.

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.