Stimulus functions of nicotine

Abstract

Behavioral pharmacology has made vital contributions to the concepts and methods used in tobacco and other drug use research, and is largely responsible for the now generally accepted notion that nicotine is the primary component in tobacco that engenders and maintains tobacco use. One of the most important contributions of behavioral pharmacology to the science of drug use is the notion that drugs can act as environmental stimuli that control behavior in many of the same ways as other stimuli (e.g., visual, gustatory, olfactory). The purpose of this chapter is to provide an overview of research that illustrates the respondent and operant stimulus functions of nicotine, using a contemporary taxonomy of stimulus functions as a general framework. Each function is formally defined and examples from research on the behavioral pharmacology of nicotine are presented. Some of the factors that modulate each function are also discussed. The role of nicotine's stimulus functions in operant and respondent theories of tobacco use is examined and some suggestions for future research are presented. The chapter illustrates how a taxonomy of stimulus functions can guide conceptions of tobacco use and direct research and theory accordingly.

Keywords: Behavior analysis; Behavioral pharmacology; Nicotine; Operant conditioning; Respondent conditioning; Stimulus functions.

Figure 1.

Mean (±SEM) response rates for intravenous infusions of nicotine (0.01 mg/kg per infusion) in rats with access to nicotine 23 hr/day. Open circles represent response rates on an active lever that produced nicotine infusions. Closed circles represent rates on an inactive lever that had no programmed consequence. The number of responses required per infusion is indicated by the fixed ratio (FR) value, which remained at FR 3 during extinction and reacquisition. Data are redrawn from LeSage, M. G., Keyler, D. E., Shoeman, D., Raphael, D., Collins, G., & Pentel, P. R. (2002). Continuous nicotine infusion reduces nicotine self-administration in rats with 23-h/day access to nicotine. Pharmacology, Biochemistry, and Behavior, 72(1–2), 279–289 with permission of the publisher.

Figure 2.

Mean (±SEM) number of responses on the active and inactive levers in rats trained to self-administer 0.06 mg/kg/infusion i.v.. The unit dose for NSA was reduced weekly until responding was within range of responding during saline extinction (S). The vertical dotted line indicates the mean threshold reinforcing unit dose (T). Significant differences from saline, ** p < 0.01, *** p < 0.001. Significant differences from 0.06 mg/kg baseline, +++ p < 0.001. Data are from Grebenstein, P. E., Burroughs, D., Roiko, S. A., Pentel, P. R., & LeSage, M. G. (2015). Predictors of the nicotine reinforcement threshold, compensation, and elasticity of demand in a rodent model of nicotine reduction policy. Drug and Alcohol Dependence, 151, 181–193 with permission of the publisher.

Figure 3.

Mean (±SEM) percentage of lever presses on the nicotine associated lever in rats trained to discriminate 0.4 mg/kg s.c. nicotine from saline at each of the indicated nicotine doses that were substituted for the training dose. Each dose-response curve was obtained in the same subjects prior to or after pretreatment with other drugs, indicating the stability of the discrimination across baseline phases. Data are from LeSage, M. G., Shelley, D., Ross, J. T., Carroll, F. I., & Corrigall, W. A. (2009). Effects of the nicotinic receptor partial agonists varenicline and cytisine on the discriminative stimulus effects of nicotine in rats. Pharmacology, Biochemistry, and Behavior, 91(3), 461–467 with permission of the publisher.