Nicotine discrimination and self-administration in humans as a function of smoking status

Abstract

Nicotine's discriminative stimulus effects may be critical to understanding reinforcement of tobacco smoking. It is not known whether regular nicotine exposure produces tolerance or sensitivity to these effects. In this study, male and female smokers (n = 11) and never-smokers (n = 10) were trained to discriminate 20 micrograms/kg nicotine by nasal spray from placebo (0) on day 1. On day 2, both groups were tested on generalization of this discrimination across intermittent presentations of 0, 3, 6, 12, and 20 micrograms/kg nicotine in random order. Quantitative and quantal behavioral discrimination tasks, used in previous research, were employed. On day 3, subjects were instructed to self-administer sprays from the 20 micrograms/kg nicotine versus 0 bottles in a concurrent-choice procedure. All but one subject (female smoker) learned reliably to discriminate 20 micrograms/kg nicotine from placebo (> or = 80% correct) on day 1. Nicotine-appropriate responding on day 2 was attenuated in smokers versus never-smokers at 20 micrograms/kg on the quantitative task and at 12 micrograms/kg on the quantal task, suggesting tolerance. There was no difference in responding at other doses. Smokers also showed attenuated responses on the subjective measure of "head rush", which was associated with discrimination responding in both groups. Nicotine self-administration was significantly greater in smokers versus never-smokers, who self-administered nicotine below chance levels, and was inversely related to discrimination behavior in never-smokers but unrelated in smokers. Women smokers showed less change in nicotine-appropriate responding across generalization doses, reported less confidence in discriminating training doses during acquisition on day 1, and tended to self-administer less nicotine on day 3. These results indicate that smokers may become tolerant to the discriminative stimulus effects of nicotine, perhaps promoting increased use.

Dose-Related Enhancement of Mood and Cognition in Smokers Administered Nicotine Nasal Spray

“…If carry-over effects were a significant factor, then dose-response functions would have been attenuated; however, we observed orderly dose-related changes on many variables. This study builds on previous research in behavioral pharmacology using cumulative or repeated dosing paradigms to determine dose-response functions within single experimental sessions (Chait et al, 1988;Perkins et al, 1997).…”

Effects of central and peripheral nicotinic blockade on human nicotine discrimination

“…A key to determining nicotine's reinforcing efficacy in humans may lie in greater knowledge of these relatively subtle interoceptive and subjective effects (Henningfield et al 1985;Stolerman and Jarvis 1995). We have found that smokers can learn to discriminate nicotine by nasal spray (Perkins et al 1994a(Perkins et al , 1996 and may develop tolerance to the interoceptive and reinforcing effects of higher nicotine doses (Perkins et al 1997).…”

“…USDHHS 1988;Perkins et al 1997). A key to determining nicotine's reinforcing efficacy in humans may lie in greater knowledge of these relatively subtle interoceptive and subjective effects (Henningfield et al 1985;Stolerman and Jarvis 1995).…”

Modeling the effect of alcohol on smoking lapse behavior

“…Human laboratory paradigms have been used to investigate various nicotine dependence phenomena such as nicotine discrimination (Perkins et al, 1997;Perkins et al, 1999), nicotine reinforcement (Perkins et al, 2001), deprivation effects (Hatsukami et al, 1984), self-administration behavior (Hatsukami et al, 1998;Perkins et al, 1997), and cue reactivity (Carter & Tiffany, 1999 for review). Researchers have also examined a human analogue of reinstatement as a model of smoking relapse, which involves a non-contingent cigarette exposure after a period of abstinence (Chornock et al, 1992;Juliano & Stitzer, 2003;King & Meyer, 2000).…”