Differential Effects of Passive Immunization with Nicotine-Specific Antibodies on the Acute and Chronic Distribution of Nicotine to Brain in Rats
Vaccination against nicotine blocks or attenuates nicotine-related behaviors relevant to addiction in rats. Passive immunization with nicotine-specific antibodies is an alternative to vaccination with the potential advantages of allowing control of antibody dose and affinity. In the current study, t...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 317; no. 2; pp. 660 - 666 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Pharmacology and Experimental Therapeutics
01.05.2006
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Subjects | |
Online Access | Get full text |
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Summary: | Vaccination against nicotine blocks or attenuates nicotine-related behaviors relevant to addiction in rats. Passive immunization
with nicotine-specific antibodies is an alternative to vaccination with the potential advantages of allowing control of antibody
dose and affinity. In the current study, the effects of two antibodies on the distribution of nicotine to brain were evaluated
during chronic nicotine administration in rats; the monoclonal antibody Nic311 ( K d = 60 nM) and nicotine-specific antiserum ( K d = 1.6 nM). Nicotine was administered via repeated i.v. bolus doses over 2 days and antibody was administered during the first
day. Neither antibody appreciably reduced the chronic accumulation of nicotine in brain, despite high protein binding of nicotine
in serum (98.9%) and a 73% reduction in the unbound serum nicotine concentration with the highest Nic311 dose. However, both
antibodies substantially reduced the early distribution of nicotine to brain 5 min after a dose. The higher affinity antibody
was no more effective than Nic311. The highest Nic311 dose produced serum antibody levels 10 times higher than those reported
with vaccination. The efficacy of Nic311 was dose-related, with the highest dose producing a 76% decrease in the early distribution
of nicotine to brain. These findings, along with previous data, suggest that the primary effect of passive immunization is
to slow, rather than prevent, the distribution of nicotine to brain. In the setting of chronic nicotine dosing, antibodies
with a moderate affinity for nicotine produced substantial effects on the early distribution of nicotine to brain and were
as effective as higher affinity antibodies. |
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ISSN: | 0022-3565 1521-0103 |
DOI: | 10.1124/jpet.105.097873 |