The discriminative stimulus and reinforcing effects of nicotine in humans following nicotine pretreatment

Abstract

Smokers often report that the first cigarette of the day is the most rewarding, and subsequent smoking is less rewarding. Reduction in smoking enjoyment later in the day may be related to acute tolerance to the discriminative stimulus effects of nicotine. We examined changes in nicotine discrimination behaviour in humans as a function of acute nicotine pretreatment. Male and female dependent smokers (n = 15) were initially trained to discriminate 20 microg/kg nicotine by nasal spray from placebo (0 microg/kg) without nicotine pretreatment. They then were tested on generalization of discrimination across a range of spray doses from 0-20 microg/kg following pretreatment with placebo, moderate dose (14-21 mg) or high dose (28-42 mg) transdermal nicotine. Generalization testing involved both two- and three-response ('novel' option) quantitative procedures. Subjects also engaged in a self-administration phase at the end of each session, involving choices between nicotine (20 microg/kg) and placebo spray. Nicotine pretreatment significantly attenuated nicotine-appropriate responding at higher nicotine spray doses, suggesting acute tolerance, but only in women. Similar results were seen for subjective 'head rush', suggesting this effect may be related to discrimination behaviour in women. However, nicotine pretreatment also increased novel-appropriate responding, especially in men, following intermediate generalization doses, suggesting qualitatively different stimulus effects. Although differences were not significant, nicotine self-administration tended to be inversely associated with nicotine pretreatment dose in men but not in women. These results only modestly support the notion of acute tolerance to the discriminative stimulus effects of nicotine, and even then only in women and not in men.

Conditioned anxiety to nicotine

“…However, it is possible that the nature of the cue elicited by this pattern of nicotine administration was insufficient to produce a conditioned response. It is also possible that after 4 weeks of exposure to nicotine the rats had habituated to the nicotine cue and that this further weakened its ability to serve as an effective conditioned stimulus, Indeed, tolerance to the discriminative stimulus effects of nicotine have been reported in smokers (Perkins et al 1997(Perkins et al , 2001. Extensive exposure to the operant chamber results in an anxiogenic effect (Irvine et al 2001a) and thus it is possible that non-specific effects of arousal, stress or anxiety interfered with conditioning to the nicotine cue.…”

NIH Electronic Cigarette Workshop: Developing a Research Agenda

“…The potential for e-cigarettes to not only deliver nicotine but also mimic the sensory aspect of smoking may be an important factor in reducing cigarette cravings in women by these devices. 99,100 As pregnant women are considered a vulnerable population, and nicotine, CO, carcinogens, and other chemicals in tobacco are reproductive toxicants, 96 the risk/benefit profile of e-cigarettes needs to be determined in this population of smokers. Of primary interest is to characterize the prevalence rates, overall nicotine exposure, cessation outcomes, and maternal and infant health outcomes of women who use e-cigarettes during pregnancy.…”

Do smokers self-administer pure nicotine? A review of the evidence

“…Fifteen dependent smokers participated in another nasal spray study (Perkins et al 2001b) that included a forcedchoice self-administration session following overnight abstinence. Prior to the self-administration procedure, participants were pretreated with a placebo, a moderate dose or a high dose transdermal nicotine patch.…”