Basic Science Investigations

Active Immunization against Nicotine Suppresses Nicotine-Induced Dopamine Release in the Rat Nucleus accumbens Shell
S.H.L. de Villiers^a, N. Lindblom^a, G. Kalayanov^b, S. Gordon^b, A. Malmerfelt^a, A.M. Johansson^b, T.H. Svensson<sup>a

a</sup>Department of Physiology and Pharmacology, Section of Neuropsychopharmacology, Karolinska Institutet, Stockholm, and
^bOrganic Pharmaceutical Chemistry, Uppsala University, Uppsala, Sweden

Address of Corresponding Author

Respiration 2002;69:247-253 (DOI: 10.1159/000063628)

  Key Words

• Nicotine
• Immunization
• Nicotine immunoconjugates
• Nucleus accumbens
• Antibody selectivity
• Dopamine

  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.

Copyright © 2002 S. Karger AG, Basel

  Author Contacts

Prof. T.H. Svensson, MD, PhD
Department of Physiology and Pharmacology
Section of Neuropsychopharmacology, Karolinska Institutet
Nanna Svartz väg 2, SE–171 77 Stockholm (Sweden)
Tel. +46 8 728 79 21, Fax +46 8 30 84 24, E-Mail torgny.svensson@fyfa.ki.se

  Article Information

Received: Received: November 6, 2001
Accepted after revision: March 4, 2002
Number of Print Pages : 7
Number of Figures : 2, Number of Tables : 1, Number of References : 43