Brain nicotinic acetylcholine receptors (nAChRs) have been implicated in the rewarding effects of ethanol and other drugs of abuse. The present study examined the effects of two important nicotinic ligands that target nAChRs, on ethanol consumption in drinking-in-the-dark or continuous access two-bottle choice drinking procedures in C57BL/6J mice. Nicotinic alkaloids such as lobeline or cytisine were administered via subcutaneous (s.c.) injections about 25 min before offering ethanol solutions. Pretreatment with lobeline (4 or 10mg/kg, s.c.) or cytisine (1.5 or 3mg/kg, s.c.) significantly reduced ethanol drinking-in-the-dark (g/kg) post 2-h and 4-h treatment, relative to control. In continuous access drinking procedure, pretreatment with lobeline (4 or 10mg/kg, s.c.) significantly reduced ethanol consumption post 1-h, 2-h, 4-h and 12-h treatment and pretreatment with cytisine (0.5, 1.5 or 3mg/kg, s.c.) significantly reduced ethanol consumption across 4-h post treatment, relative to control. Neither lobeline nor cytisine significantly affected water or sucrose solution (10% w/v) intake during drinking-in-the-dark or continuous drinking procedures, relative to control. These findings provide evidence that nAChR-mediated signaling plays a critical role in ethanol drinking behavior in mice and nicotinic ligands have therapeutic potential for cessation of binge-like ethanol drinking and dependence in humans.