Previous work has demonstrated that intake of palatable foods can alter the behavioral actions of opioid drugs. To investigate whether intake of palatable fare only affects opioid-induced behaviors or more generally influences drug-induced responses, this study examined the effects of chronic intake of a palatable sucrose solution on nicotine-induced antinociception. Eight male and eight female Long-Evans rats were provided with ground chow and water (control group), while eight males and eight females were provided with chow, water and a 32% sucrose solution (sucrose group). After 3 weeks of exposure to the dietary conditions, all rats were tested for nicotine-induced antinociception using the tail flick test. Nicotine, administered using a cumulative dose regime (0.03, 0.1, 0.3 and 1.0 mg/kg sc), led to dose-dependent increases in tail flick latencies in male and female rats. Females in the sucrose group displayed significantly greater antinociceptive responses to nicotine than those in the control group. Similar results were obtained when females were retested after an additional 2 weeks. Comparison of males and females, revealed that sucrose enhanced nicotine's antinociceptive action in female but not in male rats. While previous research suggested that sweet tasting substances might affect drug action by acting on the endogenous opioid system, the present results indicate that sucrose intake could also alter the cholinergic system and possibly other systems involved in nicotine antinociception.