Effects of nicotine in experimental animals and humans: an update on addictive properties

Tobacco use through cigarette smoking is the leading preventable cause of death in the developed world. Nicotine, a psychoactive component of tobacco, appears to play a major role in tobacco dependence, but the reinforcing effects of nicotine have often been difficult to demonstrate directly in controlled studies with laboratory animals or human subjects. Here we update our earlier review published in Psychopharmacology (Berl) in 2006 on findings obtained with various procedures developed to study dependence-related behavioral effects of nicotine in experimental animals and humans. Results obtained with drug self-administration, conditioned place preference, subjective reports of nicotine effects and nicotine discrimination indicate that nicotine can function as an effective reinforcer of drug-seeking and drug-taking behavior both in experimental animals and humans under appropriate conditions. Interruption of chronic nicotine exposure produces ratings of drug withdrawal and withdrawal symptoms that may contribute to relapse. Difficulties encountered in demonstrating reinforcing effects of nicotine under some conditions, relative to other drugs of abuse, may be due to weaker primary reinforcing effects of nicotine, to aversive effects produced by nicotine, or to a more critical contribution of environmental stimuli to the maintenance of drug-seeking and drug-taking behavior with nicotine than with other drugs of abuse. Several recent reports suggest that other chemical substances inhaled along with nicotine in tobacco smoke may play a role in sustaining smoking behavior. However, conflicting results have been obtained with mice and rats and these findings have not yet been validated in nonhuman primates or human subjects. Taken together, these findings suggest that nicotine acts as a typical drug of abuse in experimental animals and humans in appropriate situations.