Models of intravenous nicotine self-administration in laboratory animals are being used to investigate the behavioral and neurobiological consequences of nicotine reinforcement, and to aid in the development of novel pharmacotherapies for smoking cessation. Central to these models is the principle of primary reinforcement, which posits that response-contingent presentation of a primary reinforcer, nicotine, engenders robust operant behavior, whereas response-independent drug delivery does not. This dictum of nicotine as a primary reinforcer has been widely used to explain why people smoke tobacco - smoking results in the rapid delivery of nicotine to the brain, setting up a cascade of neurobiological processes that strengthen subsequent smoking behavior. However, there is mounting evidence that the primary reinforcement model of NIC self-administration fails to fully explain existing data from both the animal self- administration and human smoking literatures. We have recently proposed a """"""""dual reinforcement"""""""" model designed to more fully capture the relationship between nicotine and self-administration, including smoking. The """"""""dual reinforcement"""""""" model posits that nicotine acts as both a primary reinforcer and a reinforcement enhancer. Thus, self-administration (and smoking) is sustained by three actions: 1) nicotine, acting as a primary reinforcer, can sustain behavior that leads to its delivery;2) nicotine, acting as a primary reinforcer, can establish neutral environmental stimuli as conditioned reinforcers through Pavlovian associations;and 3) nicotine, acting as a reinforcement enhancer, can magnify the incentive value of accompanying stimuli, including nicotine-associated conditioned reinforcers. The experiment proposed below extend the testing of a model that is sensitive to both the primary reinforcing and reinforcement enhancing effects of nicotine, focusing on questions regarding the potential mechanisms by which pharmacotherapeutic interventions for smoking cessation may reduce nicotine-seeking or replace the reinforcement enhancing effects of nicotine. These questions, the answers to which will result in a much more powerful model to explore the neurobiological mechanisms of nicotine addiction and to design better smoking cessation strategies, are: (1) Do pharmacotherapeutic interventions for smoking cessation share reinforcement enhancing effects with nicotine? (2) How do pharmacotherapeutic interventions with/without reinforcement enhancing properties affect primary reinforcement by nicotine in a paradigm that can isolate this effect? The answers to these questions will establish preliminary basis for future questions about how these pharmacotherapies may affect stimuli associated with the primary reinforcing effects of nicotine.
By promoting smoking behavior, nicotine dependence increases the risk of chronic disease and mortality. Our research, which employs an animal model of nicotine use, indicates that nicotine strengthens smoking behavior because nicotine is itself rewarding and because it also makes more rewarding other aspects of smoking, including environmental stimuli associated with the behavior. The experiments proposed will continue to test this model with the long term goal of establishing its usefulness in identifying the neurobiological basis of nicotine's actions and in the development of more effective smoking cessation aids.
