Complex interactions between nicotine and nonpharmacological stimuli reveal multiple roles for nicotine in reinforcement

Rationale: Although considerable progress has been made, we do not yet fully understand the behavioral and neurobiological basis of nicotine reinforcement, and without this knowledge, treatment strategies aimed at reducing smoking remain deficient. Objectives: This review describes an original perspective on nicotine reinforcement, which arises from substantial evidence of complex interactions between nicotine and nonpharmacological stimuli. We hypothesize that nicotine reinforcement derives from at least two sources: (1) primary reinforcement, an action that requires response-dependent drug administration and is capable of conveying secondary reinforcing effects on associated stimuli, and (2) the reinforcement-enhancing effect of nicotine, which directly enhances behavior maintained by salient nonnicotine stimuli and does not require a contingent relationship between drug administration and reinforced operant responding. Although novel for nicotine, this hypothesis has origins in an extensive literature on the reinforcing effects of psychostimulants. Empirical support for this hypothesis, based largely on animal models of reinforcement, will be presented. Conclusions: Animal models of drug reinforcement have evolved to reflect our growing awareness of the multidimensional nature of drug dependence in humans. Investigating the interaction between nicotine and nonpharmacological stimuli within the context of the drug self-administration paradigm in rats has generated new insights into the paradox of how nicotine, an apparently weak primary reinforcer, can sustain the robust behavior observed in self-administration and in smoking. The hypothesis presented in this paper-that nicotine acts as both a primary reinforcer and an enhancer of other nonnicotine reinforcers-provides important direction for future investigations into the neurobiology of nicotine reinforcement and treatments for smoking cessation.