Immunization of rats reduces nicotine distribution to brain

The effect of active immunization against nicotine on the initial distribut ion of nicotine to brain was studied in anesthetized rats. Animals received nicotine 0.03 mg/kg nicotine (equivalent to the nicotine dose absorbed by a human smoking two cigarettes) as a rapid injection in the jugular vein. I n control animals, the arterial serum nicotine concentration initially exce eded the venous concentration 4.6-fold, similar to the initial arteriovenou s difference produced by cigarette smoking in humans. Animals immunized wit h the nicotine analog CMUNic maintained this arteriovenous gradient. but wi th both arterial and venous nicotine concentrations several times higher th an in controls. The arterial nicotine concentration was higher in immunized animals even at the first (7.5 s) sampling time. The brain nicotine concen tration at 3 min was 36% lower in the immunized animals. The time course of nicotine distribution to brain was studied in a second group of animals. B rain nicotine concentration was reduced in rats immunized with CMUNic over the entire 6-min sampling period immediately following nicotine dosing (mea n reduction 38%). A reduction was found at the earliest sampling time (30 s ) and was maximal at 1 min (48%). Nicotine protein binding in serum was mar kedly increased in animals immunized with CMUNic compared to controls (91.2 versus 10.9%), and the unbound nicotine concentration in serum was lower ( 10.0 versus 13.4 ng/ml). The reduction in brain nicotine concentration corr elated with antibody affinity for nicotine, and the percentage of nicotine bound in serum, These data demonstrate that nicotine-specific antibodies pr oduced by active immunization rapidly bind nicotine in arterial blood, redu ce the unbound nicotine concentration, and reduce the early distribution of nicotine to brain, Effects were observed using a clinically relevant nicot ine dose and route of administration. These data suggest that the use of im munization to modify the behavioral effects of nicotine may be possible.