The impacts of actual and perceived nicotine administration on insula functional connectivity with the anterior cingulate cortex and nucleus accumbens.

BACKGROUND: Changes in resting state functional connectivity between the insula and dorsal anterior cingulate cortex as well as between the insula and nucleus accumbens have been linked to nicotine withdrawal and/or administration. However, because many of nicotine's effects in humans appear to depend, at least in part, on the belief that nicotine has been administered, the relative contribution of nicotine's pharmacological actions to such effects requires clarification. AIMS: The purpose of this study was to examine the impacts of perceived and actual nicotine administration on neural responses. METHODS: Twenty-six smokers were randomly assigned to receive either a nicotine inhaler (4 mg deliverable) or a nicotine-free inhaler across two sessions. Inhaler content instructions (told nicotine vs told nicotine-free) differed across sessions. Resting state functional connectivity between sub-regions of the insula and the dorsal anterior cingulate cortex and nucleus accumbens was measured using magnetic resonance imaging before and after inhaler administration. RESULTS: Both actual and perceived nicotine administration independently altered resting state functional connectivity between the anterior insula and the dorsal anterior cingulate cortex, with actual administration being associated with decreased resting state functional connectivity, and perceived administration with increased resting state functional connectivity. Actual nicotine administration also contralaterally reduced resting state functional connectivity between the anterior insula and nucleus accumbens, while reductions in resting state functional connectivity between the mid-insula and right nucleus accumbens were observed when nicotine was administered unexpectedly. Changes in resting state functional connectivity associated with actual or perceived nicotine administration were unrelated to changes in subjective withdrawal and craving. Changes in withdrawal and craving were however independently associated with resting state functional connectivity between the nucleus accumbens and insula. CONCLUSIONS: Our findings highlight the importance of considering non-pharmacological factors when examining drug mechanisms of action.

The impact of anticipated and unanticipated smoking opportunities on cigarette smoking and nicotine lozenge responses.

BACKGROUND: Perceptions regarding the availability of smoking opportunities are known to affect cigarette craving; however, whether they impact actual smoking or how smokers respond to acute nicotine replacement therapy (NRT) administration is not known. This study examined the impact of pharmacological and expectancy components of NRT administration on craving and smoking in smokers anticipating or not anticipating an imminent smoking opportunity. METHODS: In total, 154 smokers (84 male) completed an experimental session in which instructions regarding the nicotine content of a lozenge (4 mg vs. no nicotine) and regarding the availability of a future smoking opportunity were manipulated. Cigarette craving was assessed before and after manipulations and lozenge administration. All participants were then allotted 1h to self-administer as many cigarette puffs as they wished. RESULTS: Unanticipated smoking opportunities reduced latency to self-administration (p<0.001), regardless of nicotine expectancy or pharmacology. When analyses included all participants, nicotine reduced intentions to smoke (p=0.016) and withdrawal-related craving (p=0.043) regardless of expectancy. Conversely, analyses using only "believers" of the nicotine content instructions revealed that nicotine expectancy reduced intentions to smoke (p=0.034) and withdrawal-related craving (p=0.047) regardless of actual nicotine administration. "Believers" also reported increased withdrawal-related craving when a smoking opportunity was perceived to be imminent (p=0.041). These effects were not significant when analyses included all participants. CONCLUSIONS: Findings suggest that unexpected smoking opportunities may be more appealing than expected ones regardless of perceived or actual acute NRT use. They also highlight the importance of reporting balanced placebo findings using all participants as well as "believers" only.

Smoking cue reactivity in current smokers, former smokers and never smokers.

INTRODUCTION: Smoking related stimuli are known to increase both subjective craving and heart rate in smokers; however, little is currently known about the effects of such stimuli in former smokers. METHODS: Subjective craving and heart rate were measured in 38 never smokers, 20 former smokers, and 30 current smokers exposed to video clips containing neutral and smoking related cues. RESULTS: Compared with neutral cues, smoking cues significantly increased both heart rate and self-reported craving in current smokers, while in former smokers smoking cues were associated with a significant decrease in heart rate as well as with a relatively diminished increase in subjective craving. Neither craving nor heart rate was impacted by the smoking cues in never smokers. CONCLUSIONS: Findings suggest that while smoking related stimuli continue to elicit modest subjective cravings in former smokers, there appears to be a marked change in the typical physiological response associated with such stimuli.

The impact of nicotine lozenges and stimulus expectancies on cigarette craving.

Reduced craving associated with nicotine replacement therapy use is frequently attributed to the effects of nicotine pharmacology, however non-pharmacological factors may also play a role. This study examined the impact of nicotine pharmacology and non-pharmacological components of an acute nicotine lozenge (4 mg) on cigarette craving, mood and heart rate in 70 daily smokers (36 male). Smoking-related stimuli were used to assess cue-induced craving. Participants were randomly assigned to one of four conditions in a balanced placebo design where half the participants were provided deceptive information regarding the nicotine content of a lozenge. Subjective ratings of craving and mood were collected and heart rate was assessed before and after neutral and smoking cues. Nicotine expectancy reduced withdrawal-related craving (p = 0.006) regardless of actual nicotine administration while combined nicotine expectancy and administration reduced intentions to smoke (p = 0.046) relative to each of the other conditions. Exposure to smoking-related stimuli increased cigarette craving (p ≤ 0.001) and negative affect (p ≤ 0.001) regardless of expectancy or pharmacology. Following the smoking cue, women reported a greater increase in withdrawal-related craving than men (p = 0.027). Findings suggest that both pharmacological and non-pharmacological components of nicotine lozenge administration contribute to its acute effects on craving, yet neither appears effective in preventing craving triggered by exposure to environmental smoking stimuli.

Sex differences in olfactory function in young patients with psychotic disorders.

Female superiority on many measures of olfactory function is well established, but debate remains as to whether this pattern extends to patients with psychotic disorders. The purpose of this large retrospective study was to re-examine whether male vs. female differences in olfactory identification exist in patients with psychotic disorders, and if so, whether any such differences were related to features of the psychotic disorder or could be explained by a generalized male-female difference. We examined 353 relatively young patients, recently diagnosed with a psychotic illness, (258 males and 95 females) and compared these with 89 healthy control subjects (45 males and 44 females). All individuals had been assessed birhinally using the University of Pennsylvania Smell Identification Test (UPSIT). Overall, females were superior to males, and patients underperformed healthy controls. No interaction was noted between these two variables, and there was no significant effect found as a result of age of the subjects. The data suggested that sex differences in olfactory identification ability exist in young patients with psychotic disorders. They do not appear to be related to exposure to antipsychotic medication or smoking habit. Therefore, it is likely that they represent basic male vs. female differences and not diagnosis-specific sex differences in olfactory performance-at least in those who are in the early stages of illness.

Unirhinal norms for the University of Pennsylvania Smell Identification Test.

Adult normative data are presented for unirhinal administration of the University of Pennsylvania Smell Identification Test (UPSIT). Two-hundred and seventy healthy adults, aged 15-64, were administered half of the UPSIT (20 items) to each nostril. The main findings were: (1) unirhinal and birhinal performance are not equivalent necessitating the use of unirhinal norms, rather than prorated birhinal norms, (2) unirhinal performance does not differ according to nostril of presentation, (3) unirhinal performance does not differ according to sex, (4) within the age ranges studied, age accounted for only a minor proportion of the variability, and (5) being a current smoker and having lower levels of formal education contributed to reduced unirhinal UPSIT scores. Correction factors are suggested for the education and smoking variables. Unirhinal evaluation may assist in further delineating the structural integrity of specific ipsilateral brain regions and potentially aid in differential diagnosis for a number of disorders.