Tissue-dependent effects of immunization with a nicotine
conjugate vaccine on the distribution of nicotine in rats.
Satoskar SD, Keyler DE, LeSage MG, Raphael DE, Ross CA, Pentel PR.
Department of Pharmacology, University of Minnesota Medical School,
Minneapolis, MN, USA. gozum002@umn.edu
Vaccination of rats against nicotine reduces nicotine distribution to brain
even at nicotine doses greatly exceeding the estimated binding capacity of
the available antibody. This observation suggests a differential effect by
which vaccination reduces nicotine distribution to brain to a greater extent
than to other tissues. To test this hypothesis, vaccinated rats received a
single intravenous nicotine dose equal to twice the estimated binding
capacity of nicotine-specific antibody in vaccinated rats. The total and
bound serum nicotine concentrations were higher in the vaccinated rats
compared to controls, while the unbound serum nicotine concentration was
lower. Distribution of nicotine to brain was reduced in vaccinated rats in a
time-dependent manner, with a greater reduction at 1 min (64%) than at 25
min (45%). Vaccination reduced nicotine distribution to muscle, testis,
spleen, liver, heart, and kidney, but to a lesser extent than to brain,
while nicotine distribution to fat was increased. Chronically infused
nicotine showed a similarly altered pattern of tissue distribution in
vaccinated rats, but differences were in general smaller than after a single
nicotine dose; brain nicotine concentration was 24% lower in vaccinated
rats, while lung nicotine concentration was higher. The presence of
nicotine-specific antibody in tissues may have contributed to the increased
nicotine concentrations in fat and lung. These data suggest that vaccination
reduces nicotine distribution to brain not only by sequestering nicotine in
serum but also by redirecting tissue distribution disproportionately away
from brain, such that nicotine concentrations are reduced to a greater
extent in brain than in other tissues.