Rethinking the nicotine stimulus

When considering human addicts, researchers often limit their definition of drug effects to those that are unconditioned, including the rewarding and reinforcing effects of drugs. Aspects of the surrounding environment, such as the paraphernalia required to consume the drug or the context in which the drug is consumed, come to be associated with these unconditioned stimulus (US) effects. The conditioned stimuli (CSs) now associated with the unconditioned drug effects come to evoke drug-related responses such as withdrawal, cravings, or desire-to-use when presented to an addicted individual, ultimately perpetuating drug abuse and precipitating relapse. Cue-exposure therapy targets these CSs and their conditioned responses (CRs). Notably, rodent models, and a sparse literature with humans, have extended this conceptualization of drug effects and conditioning processes to include a far more rich and complicated set of stimulus interactions. The basis for this extension is that drugs of abuse are interoceptive stimuli - and to an extent can function as any other stimulus can. In this review, we begin with animal models of self-administration and extinction of nicotine taking. We expand on these findings by discussing how the nicotine stimulus can come to control discriminated behaviors. Associations formed between nicotine and other stimuli in the exteroceptive environment can affect the control each has over a learned behavior. By expanding the conceptualization of the nicotine stimulus, we may be able to approach an explanation for the particularly poor success rates of cue-exposure therapy with smokers.