We examined the effect of daily administration of nicotine (0.2 mg/kg and 0.8 mg/kg, s.c.) in SD rats self-administering 20% ethanol using the method adapted from Lê (2003). Operant sessions were extended from 30 to 60 minutes using the FR3 schedule, and following 5 operant sessions, animals were separated into two balanced groups (according to ethanol intake levels in the 60 minute sessions) and assigned to either the nicotine or vehicle group. Nicotine was dissolved in saline (0.8 mg/kg, free base) and all injections were delivered via subcutaneous injection 15 minutes prior to the beginning of the daily session. Injections were given 5 days a week for 3 weeks (15 sessions) to observe the effects of chronic, high-dose nicotine pretreatment. To evaluate the effect of varenicline pretreatment on nicotine-induced increases in ethanol self-administration, varenicline was administered 30 minutes prior to the 16th and 17th nicotine pretreatment (45 minutes prior to start of the operant session). All rats received two doses (vehicle or 2 mg/kg, s.c.) over the course of 2 days in a counterbalanced design, and thus each rat served