Rationale: Immunization of rats against nicotine using a nicotine conjugate vaccine reduces the distribution of nicotine to brain in rats and attenuates some of nicotine's physiological and behavioral effects. It is not known whether such a vaccine can attenuate nicotine's reinforcing effects. Objective: The present experiment was conducted to determine whether a nicotine conjugate vaccine could interfere with the acquisition and maintenance of nicotine self-administration (NSA) in rats given 23 h day access to nicotine. Methods: To examine acquisition of NSA, rats were vaccinated with nicotine or control immunogen prior to being given access to a 0.01 mg kg-1 infusion -1 nicotine under a fixed-ratio(FR) 1 schedule for week 1, FR 2 for week 2, and FR 3 for week 3. Acquisition of cocaine self-administration (CSA) was similarly examined to determine the specificity of vaccination effects. To examine maintenance of NSA, rats were initially trained to self-administer nicotine under an FR 3 schedule, and then vaccinated with nicotine or control immunogen while NSA continued to be monitored. Results: NSA was significantly lower in vaccinated rats compared to controls during the acquisition protocol, with a 38% decrease in the number of infusions during the last week of training. The percentage of rats meeting acquisition criteria in the vaccinated group was lower (36%) than that in the control group (70%), but this difference was not statistically significant. Vaccination did not affect acquisition of CSA, demonstrating its specificity for nicotine. Maintenance of NSA was significantly reduced in vaccinated rats as compared to controls after the final vaccine injection, with a mean reduction of 57%. There was no evidence in either protocol that vaccinated rats attempted to compensate for altered nicotine distribution by increasing nicotine intake. Conclusion: These data suggest that vaccination against nicotine can reduce the reinforcing effects of nicotine in rats and may have therapeutic potential for the treatment of tobacco dependence.
Bibliographical noteFunding Information:
Acknowledgements The authors thank Cathy Ross, Heather Wendorf, Matthew Dufek, Thomas Bramwell, Sarah Polcher, and Erriane Gustaf for their technical assistance during the conduct of the study. The authors also thank Dr. Marilyn Carroll for her advice on the cocaine self-administration protocol. Yoko Heida is now at Shimane University School of Medicine, Izumo City, Japan. Greg Collins is now at the University of Michigan Medical School, Ann Arbor, MI. This research was supported by NIDA grants R01-DA10714 and U19-DA13327 and the Minneapolis Medical Research Foundation.
- Active immunization
- Nicotine-specific antibody