Clinical studies suggest that depression facilitates alcohol abuse. Depressed individuals also have increased rates of smoking, and it has been suggested that nicotine may improve depression. It is therefore possible that nicotine may reduce alcohol use in depression. To investigate this potential relationship, we evaluated alcohol intake in an animal model of depression, which consists of administering clomipramine (CLI), a preferential serotonin reuptake inhibitor, to neonatal rats. This pharmacological manipulation produces adult depression-like behaviors, such as reduced aggressiveness, decreased pleasure seeking, diminished sexual activity, increased locomotor activity and increased REM sleep. In this study, we found that CLI rats exhibited significantly higher locomotor activity, lower aggressiveness and higher alcohol intake than control rats. Chronic administration of a low dose of nicotine (0.25 mg/kg/day) or a sham operation did not modify these behaviors. However, chronic administration of nicotine at a higher dose (1.5 mg/kg/day) significantly increased aggressive behavior and reduced alcohol intake in CLI rats. The effect of nicotine on alcohol intake lasted at least 1 month after cessation of nicotine administration. These results indicate that nicotine reverted some depression signs and reduced alcohol self-administration in the CLI model of depression.