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

Abstract

Although considerable progress has been made we do not yet fully understand the behavioral and neurobiological bases of nicotine reinforcement, and without this knowledge treatment strategies aimed at reducing smoking remain deficient. This dissertation provides an original perspective on nicotine reinforcement, which arises from substantial evidence of complex interactions between nicotine and nonpharmacological stimuli. The present experiments tested the hypothesis that nicotine reinforcement derives from at least two sources: 1) the primary reinforcing properties of nicotine, an action that requires response-dependent drug administration, and 2) the more prominent ability of nicotine to enhance behavior maintained by salient non-nicotine stimuli, an action that 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 properties of psychostimulant drugs. Empirical support for the application of this hypothesis to nicotine reinforcement will be presented. By investigating the interaction between nicotine and nonpharmacological stimuli within the context of drug selfadministration in rats, the present research has generated new insights into the paradox of how nicotine, an apparently weak primary reinforcer, can sustain the robust behavior observed in selfadministration and in smoking. Hypotheses generated by these data provide important direction for future investigations into the neurobiology of nicotine reinforcement.iii

Metabotropic Glutamate 5 Receptor (mGluR5) Antagonists Decrease Nicotine Seeking, But Do Not Affect the Reinforcement Enhancing Effects of Nicotine

“…First, nicotine directly strengthens operant responding (primary reinforcing effect, see Chaudhri et al, 2006). Second, nicotine enhances the incentive value of reinforcing nonpharmacological stimuli Donny et al, 2003;Palmatier et al, 2006).…”

Associations between Cloninger's temperament dimensions and acute tobacco withdrawal

“…For example, Elovainio et al (2005) demonstrated that the effect of dopamine D4 receptor genotype on smoking behavior was mediated by NS. Third, systems involved in processing and responding to appetitive, aversive, and novel stimuli that are related to TCI temperament dimensions may also underlie smoking behavior (Chaudhri et al, 2006). Specifically, responding to aversive stimuli, such as the physical sensations of nicotine withdrawal, may be exaggerated in individuals with particular TCI profiles.…”

Sex differences in nicotine levels following repeated intravenous injection in rats are attenuated by gonadectomy

“…Persistent use and dependence on tobacco is mediated primarily, but not exclusively, by nicotine (Chaudhri et al, 2005b;Wonnacott et al, 2005). Sex is an important factor that mediates the neurobiological response to nicotine, and ultimately the course of dependence behavior in humans that abuse cigarettes.…”