Self-Administration of Smokeless Tobacco Products in Rats

Abstract

Objective: Preclinical abuse liability assessment is an essential component of tobacco regulatory science. The goal of this project was to evaluate the relative abuse liability of smokeless tobacco products in rats using aqueous extracts of those products. These extracts provide exposure to an extensive range of nicotine and non-nicotine tobacco constituents as occurs in humans.

Methods: Rats were trained to self-administer either nicotine alone or extracts of Camel Snus or Kodiak smokeless tobacco at an equivalent nicotine unit dose. In Experiment 1, the relative reinforcing efficacy of these formulations was assessed in adults and adolescents using a progressive ratio schedule under limited-access conditions. In Experiment 2, relative reinforcing efficacy was assessed in adolescents under unlimited-access conditions using behavioral economic demand curve analysis.

Results: The reinforcing efficacy of nicotine formulations was higher in adolescents than adults, but no difference was observed between formulations in either age group. Similarly, there was no difference in elasticity of demand between formulations in adolescents.

Conclusions: The present findings suggest that the abuse liability of these smokeless tobacco products is similar to nicotine alone, and that nicotine dose is the primary determinant of the reinforcing efficacy of systemic exposure to these products.

Keywords: abuse liability; behavioral economics; nicotine; progressive-ratio schedule; rat; self-administration; smokeless tobacco extracts.

Appendix A. Daily Responding During the Acquisition Phase of Experiment 1

Note. Mean (±SEM) responses on the active and inactive lever on consecutive sessions during the acquisition phase of Experiment 1 in each age group for each indicated formulation.

Appendix B. Daily Responding During the Acquisition Phase of Experiment 2

Note. Mean (±SEM) responses on the active and inactive lever on consecutive sessions during the acquisition phase of Experiment 2 for each indicated formulation.

Figure 1. Mean Responding on the Active and Inactive Levers During the Acquisition Phase of Experiment 1

Note. Mean (± SEM) responses on the active and inactive lever in each group of adolescent and adult rats across the last three session under the FR 1 schedule in Experiment 1. Different from saline, +p < .05, +++p < .001. Different from inactive lever, ***p < .001.

Figure 2. Mean Infusions During the Acquisition and Progressive-Ratio Phases of Experiment 1

Note. Mean (± SEM) infusions earned per session in each group of adolescent and adult rats across the last three sessions under the FR 1 schedule in Experiment 1 are shown in the left panel. Mean (± SEM) breaking points (expressed as infusions on the left y-axis and associated last completed FR on the right y-axis) across the last three sessions under the PR schedule in Experiment 1 are shown in the right panel. No saline data are shown for the PR schedule because data were only analyzed for rats that met acquisition criteria. Main effect of age, **p < .01. Different from saline, ++p < .01, +++p < .001. Different from nicotine, #p < .05.

Figure 3. Mean Responses, Infusions, and Exponential Demand Curves During Experiment 2

Note. Mean (± SEM) responses on the active and inactive lever (panel A) and mean (± SEM) infusions earned per session (panel B) in each group of adolescent rats during the last three sessions under the FR 1 schedule in Experiment 2. Panel C shows nicotine consumption in each group as a function of unit price with associated exponential demand curve fits during demand curve assessment in Experiment 2. Individual and group demand parameter estimates are shown in Table 1. Different from saline (panel A), ***p < .001. Different from saline (panel B), *p < 0.05, **p < 0.01.