The utility of an animal model is predicated on its ability to incorporate essential features of the human phenomenon it is modeling in a way that permits systematic investigation of those features. For this reason, investigators who study the neurobiological mechanisms of addictive drugs such as opiates and stimulants are making extensive use of self-administration models as a way to more closely mimic the manner in which drugs of abuse are experienced by humans (Bozarth, Murray, & Wise, 1989; Caggiula, Donny, White, Chaudhri, Booth, Gharib, Hoffman, Perkins, & Sved, 2001; Carroll, Krattiger, Gieske, & Sadoff, 1990; Corrigall & Coen, 1989; Donny, Caggiula, Knopf, & Brown, 1995; Johanson, 1981; Roberts, 1992; Shaham & Stewart, 1995). A basic tenet of the self-administration model is that a drug, acting as a primary reinforcer, will increase the future occurrence of a response if its administration is contingent on that response (Meisch, 1993). Nicotine, like other drugs of abuse, is self-administered by a variety of animal species (Corrigall & Coen, 1989; Goldberg, Spealman, & Goldberg, 1981; Henningfield & Goldberg, 1983; Rose & Corrigall, 1997). Nicotine self-administration is dose- and schedule-dependent (Corrigall & Coen, 1989; Donny, Caggiula, Mielke, Jacobs, Rose, & Sved, 1998; Donny, Caggiula, Rowell, Gharib, Maldovan, Booth, Mielke, Hoffman, & McCallum, 2000; Shoaib, Schindler, & Goldberg, 1997), extinguishes when nicotine is removed (Corrigall & Coen, 1989; Taylor & Jentsch, 2001), and is dependent on nicotine delivery being response-contingent (Donny et al., 1998). Models of nicotine self-administration are being used to investigate the behavioral, environmental and neurophysiological underpinnings of nicotine reinforcement (e.g., Caggiula et al., 2001; Corrigall, 1992; Picciotto, Zoli, Rimondini, Lena, Marubio, Pich, Fuxe, & Changeux, 1998) and to aid in the development of novel pharmacotherapies for smoking cessation.
However, there is mounting evidence that a simple, primary reinforcement model of nicotine 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 (Chaudhri, Caggiula, Donny, Palmatier, Liu, & Sved, 2006b; Donny, Chaudhri, Caggiula, Evans-Martin, Booth, Gharib, Clements, & Sved, 2003) that is designed to more fully capture the relationship between nicotine and self-administration in animals and smoking in humans. This model incorporates a large body of evidence that emphasizes the importance of non-nicotine stimuli that accompany nicotine delivery and contribute to the overall level of reinforcement afforded to the behavior. The model addresses the nature of the relationship between such stimuli and nicotine, and it postulates that the resulting behavior is a function of nicotine acting as both a primary reinforcer and an enhancer of the incentive motivational and reinforcing effects of accompanying stimuli. We will first briefly discuss the importance of non-nicotine stimuli in self-administration and smoking. We will then outline our model describing the two ways in which nicotine interacts with those stimuli and discuss the research conducted to test the major tenets of the model (see Table 6.1).