The Reinforcing Effects of Nicotine in Humans and Nonhuman Primates: A Review of Intravenous Self-Administration Evidence and Future Directions for Research

Cigarette smoking is largely driven by the reinforcing properties of nicotine. Intravenous (IV) self-administration procedures are the gold standard for investigating the reinforcing effects of psychoactive drugs. The goal of this review was to examine the results of published investigations of the reinforcing effects of nicotine measured using IV self-administration procedures in humans and nonhuman primates. The body of literature using nonhuman primate subjects indicates nicotine functions as a positive reinforcer when available for self-administration via IV catheters. However, it can also be difficult to establish IV nicotine self-administration in nonhuman primates and sometimes supplemental strategies have been required (e.g., priming injections or food deprivation) before subjects acquire the behavior. Although the body of literature using human subjects is limited, the evidence indicates nicotine functions as a reinforcer via the IV route of administration in adult cigarette smokers. Rates of nicotine self-injection can be variable across subjects and responding is sometimes inconsistent across sessions in both humans and nonhuman primates. The Family Smoking Prevention and Tobacco Control Act, enacted in 2009, gave the Food and Drug Administration regulatory authority over the manufacture, marketing, and distribution of tobacco products. Research examining the threshold reinforcing doses for initiation and maintenance of nicotine self-administration, comparisons of the reinforcing effects of nicotine in adolescent versus adult subjects, investigations of gender differences in the reinforcing effects of nicotine, and studies of the abuse liability of non-nicotine tobacco product constituents and their ability to alter the reinforcing effects of nicotine will inform potential tobacco regulatory actions.