Mood, nicotine, and dose expectancy effects on acute responses to nicotine spray.

INTRODUCTION: We recently showed effects of nicotine dose and nicotine expectancy on some responses to cigarette smoking, with generally no influence of induced mood on these effects. The present study extended this line of research to Nicotrol nasal spray, to determine whether formulation (spray vs. smoking) alters responses. METHODS: Smokers abstained overnight before each of two virtually identical sessions, involving negative or positive mood induction. They were randomized to one of five groups, four comprising the 2 x 2 balanced placebo design, varying actual and expected dose of nicotine in the nasal spray, and the fifth group a no-spray control. Dependent measures included self-reported affect, craving, withdrawal, and spray ratings of "liking" and "how much nicotine." Analyses were limited to those whose nicotine expectancies were manipulated successfully (N = 48). RESULTS: The following results matched those from our smoking study: expecting nicotine increased liking; expected, but not actual, nicotine dose increased dose perception; neither actual nor expected nicotine dose had much influence on affect or withdrawal; and mood had no influence on these effects. However, both actual and expected nicotine dose decreased craving in response to spray, contrary to our prior study with smoking. DISCUSSION: Formulation made little difference in some effects of nicotine and expectancies, but other effects differed by formulation. Some of these findings, particularly for craving reduction, may have implications for enhancing the acute therapeutic effects of nasal spray and, perhaps, other medications in smokers trying to maintain abstinence after quitting.

Mood influences on acute smoking responses are independent of nicotine intake and dose expectancy.

Acute responses to smoking are influenced by nicotine and by nonpharmacological factors such as nicotine dose expectancy and sensory effects of smoke inhalation. Because negative mood increases smoking reinforcement, the authors examined whether these effects may be altered by mood context. Smokers (n=200) participated in 2 sessions, negative or positive mood induction, and were randomized to 1 of 5 groups. Four groups comprised the 2x2 balanced placebo design, varying actual (0.6 mg vs. 0.05 mg yield) and expected nicotine dose (expected nicotine vs. denicotinized [denic]) of cigarettes. A fifth group was a no-smoking control. Smoking, versus not smoking, attenuated negative affect, as well as withdrawal and craving. Negative mood increased smoking reinforcement. However, neither actual nor expected nicotine dose had much influence on these responses; even those smokers receiving and expecting a denic cigarette reported attenuated negative affect. A follow-up comparison suggested that the sensory effects of smoke inhalation, but not the simple motor effects of smoking behavior, were responsible. Thus, sensory effects of smoke inhalation had a greater influence on relieving negative affect than actual or expected nicotine intake.

Sex differences in the influence of nicotine dose instructions on the reinforcing and self-reported rewarding effects of smoking.

RATIONALE: Compared to men, the smoking behavior of women may be less responsive to nicotine and more responsive to nonpharmacological factors, perhaps including verbal information (e.g., dose instructions). OBJECTIVE: This study compared the influence of the presence vs absence of dose instructions on the subjective and reinforcing effects of nicotine via cigarette smoking in men and women. METHODS: Subjects (n=120) abstained overnight from smoking and were randomly assigned to one of four groups. Half of the subjects received nicotine cigarettes (Quest 1, yield of 0.6 mg), and the other half received denicotinized cigarettes ("denic"; Quest 3, yield of 0.05 mg). Furthermore, half of each subsample was accurately instructed they were receiving a "normal nicotine" or a "no nicotine" cigarette, while the other half received no instructions. Subjects completed baseline measures of craving and mood (positive and negative affect), took two puffs from the cigarette after receiving dose instructions or no instructions, and then rated the cigarette's "reward" value (liking, satisfying) and other characteristics. They also repeated the craving and mood measures. Subjects then smoked more of that same brand ad libitum over the next 30 min to measure reinforcement (puff number and latency to first puff). RESULTS: Overall, nicotine increased reward, other cigarette ratings, and positive affect, but did not affect craving or smoking behavior. However, results varied by sex. Dose instructions enhanced the effects of nicotine on smoking reward and reinforcement in women, while instructions tended to dampen or even reverse these effects of nicotine in men (i.e., interaction of sex x nicotine x instructions). CONCLUSIONS: In women but not in men, the influence of nicotine on smoking reward and reinforcement is enhanced by accurate verbal information about the cigarette's nicotine dose. These results are consistent with the notion that the smoking behavior of women, relative to men, may be more responsive to nonpharmacological factors.

The subjective and reinforcing effects of visual and olfactory stimuli in alcohol drinking.

Nonpharmacological cues associated with drug intake may influence subjective and reinforcing effects of those drugs. Social drinkers (N = 80) participated in 2 sessions in which they rated and then consumed ad lib their preferred beer (with participants blind to brand). Visual and olfactory stimuli were obscured during 1 session (blocked) and not obscured during the other (unblocked). Dependent measures included ratings of "liking", "want another", and "desire to drink"; subjective mood; and ad lib beer consumption (reinforcement). Most ratings and ad lib consumption were lower during the blocked versus the unblocked condition. There were no interactions of blockade condition with sex and no effect of blockade on mood. These findings show that nonpharmacological stimuli associated with alcohol consumption influence alcohol's subjective and reinforcing effects.

The influence of instructions and nicotine dose on the subjective and reinforcing effects of smoking.

Subjective and reinforcing effects of smoking a cigarette were examined within a 2 x 2 modified balanced-placebo design, which manipulated instructions about nicotine content (i.e., told regular nicotine vs. told low nicotine) and actual nicotine dose (given a regular nicotine brand vs. a denicotinized brand). Most ratings of the nicotine content and reward value of cigarettes were higher for those told regular nicotine versus told low nicotine, and for those given regular nicotine versus given low nicotine. Nicotine and instructions did not affect craving, withdrawal, or smoke-reinforced responding, but instructions affected the number of puffs earned for those given low nicotine (i.e., placebo effect). Thus, verbal information (instructions) can influence some responses to smoking consistent with the presence of placebo and antiplacebo effects.

Dopamine and opioid gene variants are associated with increased smoking reward and reinforcement owing to negative mood.

Negative mood increases smoking reinforcement and risk of relapse. We explored associations of gene variants in the dopamine, opioid, and serotonin pathways with smoking reward ('liking') and reinforcement (latency to first puff and total puffs) as a function of negative mood and expected versus actual nicotine content of the cigarette. Smokers of European ancestry (n=72) were randomized to one of four groups in a 2x2 balanced placebo design, corresponding with manipulation of actual (0.6 vs. 0.05 mg) and expected (told nicotine and told denicotinized) nicotine 'dose' in cigarettes during each of two sessions (negative vs. positive mood induction). Following mood induction and expectancy instructions, they sampled and rated the assigned cigarette, and then smoked additional cigarettes ad lib during continued mood induction. The increase in smoking amount owing to negative mood was associated with: dopamine D2 receptor (DRD2) C957T (CC>TT or CT), SLC6A3 (presence of 9 repeat>absence of 9), and among those given a nicotine cigarette, DRD4 (presence of 7 repeat>absence of 7) and DRD2/ANKK1 TaqIA (TT or CT>CC). SLC6A3, and DRD2/ANKK1 TaqIA were also associated with smoking reward and smoking latency. OPRM1 (AA>AG or GG) was associated with smoking reward, but SLC6A4 variable number tandem repeat was unrelated to any of these measures. These results warrant replication but provide the first evidence for genetic associations with the acute increase in smoking reward and reinforcement owing to negative mood.