Effects of adolescent nicotine exposure and withdrawal on intravenous cocaine self‐administration during adulthood in male C57BL/6J mice

Studies of adolescent drug use show (1) a pattern in which the use of tobacco precedes the use of other drugs and (2) a positive relationship between adolescent tobacco use and later drug use. These observations have led to the hypothesis that a causal relationship exists between early exposure to nicotine and the later use of hard drugs such as cocaine. Using male C57BL/6J mice, we tested the hypothesis that nicotine exposure in adolescence leads to increased intravenous self‐administration ( IVSA ) of cocaine in adulthood. Using miniature osmotic pumps, we exposed mice and their littermate controls to nicotine (24 mg/kg/day) or vehicle, respectively, over the entire course of adolescence [postnatal days ( P ) 28–56]. Nicotine exposure was terminated on P 56 and mice were not exposed to nicotine again during the experiment. On P 73, mice were allowed to acquire cocaine IVSA (1.0 mg/kg/infusion) and a dose–response curve was generated (0.18, 0.32, 0.56, 1.0, 1.8 mg/kg/infusion). Lever pressing during extinction conditions was also evaluated. All mice rapidly learned to lever press for the combination of cocaine infusions and non‐drug stimuli. Analysis of the dose–response curve revealed that adolescent nicotine‐exposed mice self‐administered significantly more ( P  < 0.05) cocaine than controls at all but the highest dose. No significant differences were observed between adolescent nicotine‐exposed and control mice during the acquisition or extinction stages. These results indicate that adolescent nicotine exposure can increase cocaine IVSA in mice, which suggests the possibility of a causal link between adolescent tobacco use and later cocaine use in humans.