Active immunization against nicotine suppresses nicotine-induced dopamine release in the rat nucleus accumbens shell.

Abstract

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.

• Authors: S H L de Villiers, N Lindblom, G Kalayanov, S Gordon, A Malmerfelt, A M Johansson, T H Svensson
• Journal: Respiration; international review of thoracic diseases (Respiration) Vol. 69 Issue 3 Pg. 247-53 ( 2002) ISSN: 0025-7931 [Print] Switzerland
• PMID: 12097769 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2002 S. Karger AG, Basel

Chemical References

• Immunoconjugates
• Nicotinic Agonists
• Vaccines, Conjugate
• Nicotine
• Hemocyanins
• keyhole-limpet hemocyanin
• Dopamine

Topics

• Animals
• Dopamine (metabolism)
• Enzyme-Linked Immunosorbent Assay
• Hemocyanins
• Immunoconjugates
• Male
• Nicotine (analogs & derivatives)
• Nicotinic Agonists (pharmacology)
• Nucleus Accumbens (drug effects, metabolism)
• Rats
• Tobacco Use Disorder (prevention & control)
• Vaccination (methods)
• Vaccines, Conjugate (pharmacology, therapeutic use)