Active immunization against nicotine suppresses nicotine-induced dopamine release in the rat nucleus accumbens shell.
BACKGROUND
Tobacco smoking is the largest preventable cause of morbidity and premature mortality in the world. Although its medical consequences are well documented, 20-50% of the population even in developed countries remain tobacco smokers. The drugs presently used in smoking cessation have limited efficiency and, therefore, there is a need for alternative and improved treatments. One novel approach in this regard may be provided by immunization against nicotine.


OBJECTIVE
The present study in male Wistar rats investigated if active immunization with a novel nicotine immunogen, IP18-KLH, may generate nicotine-selective antibodies and, furthermore, whether this treatment might prevent nicotine from exerting its stimulating effect on the mesolimbic, dopaminergic reward system in the brain.


METHODS
Enzyme-linked immunosorbent assay (ELISA) was used to determine the titer of nicotine antibodies in plasma after immunization with IP18-KLH in Freund's adjuvant. Competitive ELISA was used to assess the selectivity of the antibodies. Finally, we used in vivo voltammetry to investigate whether active immunization with IP18-KLH could prevent nicotine-induced dopamine release in the shell of nucleus accumbens (NAC(shell)).


RESULTS
The present study shows that active immunization with IP18-KLH generates antibodies that are highly selective for nicotine. Furthermore, immunization with IP18-KLH prevented the nicotine-induced increase in dopamine release in the NAC(shell), a biochemical correlate to the rewarding properties of nicotine.


CONCLUSIONS
Active immunization with IP18-KLH prevents a central effect of nicotine that is considered critical for the induction of nicotine dependence. Consequently, active immunization may provide long-term protection against initiation of tobacco dependence, an effect that may prove particularly advantageous in relapse prevention.
de Villiers
S H L
SH
Department of Physiology and Pharmacology, Section of Neuropsychopharmacology, Karolinska Institutet, Stockholm, Sweden.
Lindblom
N
N
Kalayanov
G
G
Gordon
S
S
Malmerfelt
A
A
Johansson
A M
AM
Svensson
T H
TH
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006433:Hemocyanins; D018796:Immunoconjugates; D008297:Male; D009538:Nicotine / Q000031:analogs & derivatives*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D014029:Tobacco Use Disorder / Q000517:prevention & control; D014611:Vaccination / Q000379:methods*; D018074:Vaccines, Conjugate / Q000494:pharmacology* / Q000627:therapeutic use
D018796:Immunoconjugates; D018722:Nicotinic Agonists; D018074:Vaccines, Conjugate; D009538:Nicotine; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D004298:Dopamine