Regulation of Intravenous Nicotine Self-Administration — Dopamine Mechanisms

Summary

Intravenous self-administration of nicotine has been obtained in rats with a limited-access model. Nicotine is a powerful reinforcer in this situation. Dependency upon dose is greatest at high and low ends of the dose range, but responding is relatively insensitive to dose at mid-range values; this is similar to the dependency of cigarette smoking behavior on nicotine delivery. The role of dopamine in nicotine reinforcement has been examined using this self-administration paradigm. Selective D1 (SCH23390) and D2 (spiperone) dopamine antagonists reduce nicotine self-administration in a dose-dependent fashion. The same dose range of D1 and D2 antagonists produce compensatory increases in cocaine self-administration. These differences in the effects of dopamine antagonists may stem from the different regulation of nicotine as compared to cocaine. Lesions of the mesolimbic dopamine system made by microinfusions of the neurotoxin 6-hydroxydopamine into the nucleus accumbens attenuate both nicotine self-administration and food-maintained behavior. These data suggest that dopamine mechanisms, perhaps in the mesolimbic system, play a role in nicotine reinforcement.